Home Life Sciences Role of cerebellar cortex in associative learning and memory in guinea pigs
Article Open Access

Role of cerebellar cortex in associative learning and memory in guinea pigs

  • Rui Li , Qi Li , Xiaolei Chu , Lan Li , Xiaoyi Li , Juan Li , Zhen Yang EMAIL logo , Mingjing Xu , Changlu Luo and Kui Zhang EMAIL logo
Published/Copyright: September 14, 2022
Download Article (PDF)
Open Life Sciences
From the journal Open Life Sciences Volume 17 Issue 1

Abstract

Time-related cognitive function refers to the capacity of the brain to store, extract, and process specific information. Previous studies demonstrated that the cerebellar cortex participates in advanced cognitive functions, but the role of the cerebellar cortex in cognitive functions is unclear. We established a behavioral model using classical eyeblink conditioning to study the role of the cerebellar cortex in associative learning and memory and the underlying mechanisms. We performed an investigation to determine whether eyeblink conditioning could be established by placing the stimulating electrode in the middle cerebellar peduncle. Behavior training was performed using a microcurrent pulse as a conditioned stimulus to stimulate the middle cerebellar peduncle and corneal blow as an unconditioned stimulus. After 10 consecutive days of training, a conditioned response was successfully achieved in the Delay, Trace-200-ms, and Trace-300-ms groups of guinea pigs, with acquisition rates of >60%, but the Trace-400-ms and control groups did not achieve a conditioned stimulus-related blink conditioned response. It could be a good model for studying the function of the cerebellum during the establishment of eyeblink conditioning.

Keywords: cerebellar cortex; delay eyeblink conditioning; lateral pontine nuclei; middle cerebellar peduncle; trace eyeblink conditioning

1 Introduction

The classic eyeblink conditioning combines events associated with time cognition using conditioned stimulus and unconditioned stimulus and, therefore, is widely used as an associative learning and memory model for studying the mechanisms of temporal information processing in specific brain areas [1,2]. Delay and trace conditioning are distinguished not by the interval between stimuli, which can be identical, but by the difference in the offset of the stimuli. In trace conditioning, the onset and offset of the conditioned stimulus occur before the onset of the unconditioned stimulus, and there is a gap (or “trace”) between them. In delay conditioning, the onset between the conditioned and unconditioned stimuli is different, but the offset is usually the same, i.e., they end together, and there is an overlap between the two stimuli. The two behavioral models differ according to the presence of a time interval between stimuli. As a result, there is a gap between the onsets of the conditioned and unconditioned stimuli. The length of this gap can be used to study the ability of specific brain areas to process information related to temporal information processing.

Patients with autism spectrum disorders [3], cerebellar diseases [4], cerebellar degeneration [5], migraine [6], fetal alcohol syndrome [7], schizophrenia [8,9], severe depression [10], and other neuropsychiatric disorders [11,12,13] all show the abnormal ability of temporal information processing. Thus, using the eyeblink conditioning model to study the brain areas involved in temporal information processing would help to understand further the neurobiological mechanism of time-related learning and memory in mammalian animals [14,15].

Previous studies have suggested that temporal information processing mainly occurs in cerebral neural circuits, including the thalamus, cerebral cortex, medial prefrontal cortex, and hippocampus [16,17,18]. In addition, similar to the cerebral cortex, the cerebellum also exerts advanced functions in temporal information processing. Indeed, patients with cerebellar injury develop motor sequence learning disorders [19,20], suggesting the importance of the cerebellum in time estimation. In addition, neuroimaging studies have shown significant differences in the area of cerebellar activation before and after sequence training and learning [21,22]. Cerebellar lesions can lead to a wide range of clinical cognitive impairments, and the most common is impaired temporal information processing [23,24]. In addition, pathological changes in cerebellar disorders, including cerebellar hypoplasia [25], space-occupying intracranial lesions [26,27], and trauma [26], among others, can also lead to dysfunction or loss of temporal information processing-related abilities. Animal experiments have shown that decerebrated guinea pigs (the cerebral cortex and subcortical hippocampus were removed completely, and only the brainstem and cerebellum were left) still acquired conditioned responses [28]. Recordings of basket cell discharge have shown that the activation of certain cerebellar neurons is closely associated with classical eyeblink conditioning [29,30,31]. In addition, physical damage to the cerebellar cortex significantly inhibits the ability of rabbits to establish eyeblink conditioning [32,33,34,35,36,37,38,39]. These results all demonstrate that the cerebellum is closely related to temporal information processing, but whether it independently participates in temporal information processing in associative learning and memory is still controversial. Therefore, exploring the role of the cerebellar cortex in associative learning and memory would help understand the mechanism of specific brain areas in handling time-related events. Based on the foregoing, this issue has attracted considerable research in the field of neuroscience.

Classical eyeblink conditioning often uses peripheral sensory stimuli as the conditioned stimulus and conducts the signal via visual or auditory pathways to the thalamus, cerebral cortex, or medial prefrontal cortex. With respect to eyeblink conditioning established via the forebrain–cerebellum circuit, the conditioned stimulus is often affected by many external factors, and this limits the study of specific brain areas in related neural circuits. Since neurons or circuits can hardly be analyzed specifically, determining whether the cerebellar cortex is directly involved in associative learning and memory is therefore difficult. Neuroanatomy has shown that the middle cerebellar peduncle, with mossy fiber as its main component, is one of the major afferent fibers in the cerebellar cortex. It is constituted by the pontine-cerebellar fiber derived from the lateral pontine nucleus, and it ends at the cerebellar cortex [40].

At present, it is still unclear how mammals connect two independent events based on time and by which neurobiological mechanism they process related information and take appropriate action within the corresponding time [41,42]. The eyeblink conditioning model has been widely used in exploring the mechanism of certain brain areas in learning and memorizing [43]. As previously used by several authors and studies, we used microcurrent pulse and photosensitive receptors to substitute traditional sound and light as the conditioned stimulus to directly stimulate the middle cerebellar peduncle and used corneal blow as the unconditioned stimulus, as previously described for different parts of the brain [18,44,45,46,47,48]. This design successfully established a delay eyeblink conditioning model and trace eyeblink conditioning models within a certain time interval range. Our results suggested that the cerebellar cortex could accomplish the process of associative learning and memory independently for time-related events. A similar approach was used by Steinmetz et al. [49], who showed conditioned blinks using mossy fiber stimulation in the rabbit, and by Swain, Shinkman, and Thompson in the 1990s [50], who used electrical stimulation of the cerebellar cortex to mediate conditioned eyeblinks in the rabbit.

Thus, this study aimed to use a microcurrent pulse to directly stimulate the middle cerebellar peduncle and observe whether the cerebellar cortex could establish an eyeblink conditioning independently, and analyze the cerebellum’s role in recognizing time in Guinea pigs. Using induced action potential on mossy fiber as the conditioned stimulus, we prevented persistent neuronal activity generated from mixed information input to different forebrain structures and, therefore, avoided this influence on the establishment of eyeblink conditioning. Briefly, this study substituted traditional sound and light stimuli with electrophysiology as the conditioned stimulus. It also investigated whether the cerebellar cortex could establish eyeblink conditioning and its amplitude under such stimulation. By doing this, we further revealed the role and mechanism of the cerebellar cortex in associative learning and memory. This study provides conclusive evidence for the function of the cerebellum in advanced temporal information processing. Our study will facilitate the application of neurobiology in clinical diagnosis and treatment. It will also provide a theoretical foundation for managing cerebellar cognitive dysfunction, particularly temporal information processing. This study could help determine the impact of the location of an injury on cognitive behavior and infer whether the lesion location could impact the prognosis. Eyeblink conditioning was used in previous studies of various medical conditions [11,12,13].

2 Materials and methods

2.1 Experimental animals

The animals were provided by the Laboratory Animal Center (license #SCXK (Chongqing) 2007-0001). Male guinea pigs aged 4–5 months, weighing 400–450 g and without obvious eye diseases, were selected for electrode neuronal stimulation. All animals were kept separately in cages with dry sawdust matting and free access to food and water. Animals were reared in an environment of 20–25°C temperature, 50–80% relative humidity, and a 12/12 h light-dark cycle.

  1. Ethical approval: The research related to animal use has been complied with all the relevant national regulations and institutional policies for the care and use of animals, and was approved by the Ethics Committee of Guizhou Provincial People’s Hospital (No. 2015014).

2.2 Intracranial implantation of the stimulating electrode

Guinea pigs were anesthetized by intraperitoneal injection of ketamine (80 mg/kg) and phenothiazine (5 mg/kg). Thirty guinea pigs were selected for implantation shocks. The guinea pigs were divided into (1) delay group, (2) Trace-200ms group, (3) Trace-300ms group, (4) Trace-400ms group, and (5) control group, with six animals per group, 30 in total. In the end, one animal in the Trace-200ms group and one in the Trace-400ms group were implanted with electrodes but their placement was incorrect. Therefore, 28 guinea pigs were included in the final behavioral groups: (1) Delay group, n = 6; (2) Trace-200ms group, n = 5; (3) Trace-300ms group, n = 6; (4) Trace-400ms group, n = 5; and (5) control group, n = 6. For electrode implantation, the head was fixed in a stereotactic apparatus (SR-6N, Narishige Scientific Instrument, Japan). Then, using the bregma suture as the zero-reference point, a welded stimulating electrode (A-M Systems, Sequi, USA, external diameter: 0.7 mm, coating diameter: 330.2 mm, and internal diameter: 0.254 mm) was implanted into the brain at 15 mm posterior to the bregma, 3.5 mm laterally (left) from the midline, and 7 mm ventrally from the bregma line. The electrode tip was fixed using dental cement in the left middle cerebellar peduncle. A reference electrode was also implanted in the left middle cerebellar peduncle. The guinea pigs were observed for 1 week after surgery. Those with no significant infection and high activity were taken for behavior training.

2.3 Behavior training

Thirty male guinea pigs that successfully underwent the implantation were randomized (lottery method) into the experimental groups (Delay, Trace-200ms, Trace-300ms, and Trace-400ms groups) and the control group (n = 6/group). According to whether there was a fixed time relationship between CS and US, they were divided into the experimental and control groups. According to the time interval (trace interval, TI) between CS and US, they were divided into the (1) the Delay group, (2) Trace-200ms group, (3) Trace-300ms group, and (4) Trace-400ms group, for a total of five groups (including the control group) with six animals in each group. For adaptation, all guinea pigs were placed in a shielding cabinet with light and sound insulation for 2 days, 60 min each day, without any stimulation. After adaptation, the animals underwent 10 consecutive days of behavior training, with a session of 100 stimulations each day. A given animal was trained at the same time each day. A conditioned stimulus was produced using a microcurrent pulse generated from a YC-2 stimulator (Chengdu Instrument, China) and an isolation unit (ISO-Flex, AMPI, Israel) to stimulate the right middle cerebellar peduncle. The output intensity was min 40%, which could initiate a blink reaction (based on the preliminary experiment, this was obtained by increasing the output intensity until eyelid closing could be measured). For the electrical stimulations, the waveform was a train of 0.1 ms pulses delivered at 200 Hz for 350 ms. The waveform was a square wave, and the pulse was a 200 Hz series of single-pulse current (pulse interval time: 4.9 ms, single pulse width: 0.1 ms, and pulse: 70 groups). A 100-ms pure oxygen flow was used as the unconditioned stimulus, and the outlet pressure was strictly adjusted to 3 psi by a pressure-reducing valve. The time interval for trace eyeblink conditioning is shown in Figure 1 for the different experimental groups. For the control group, the time interval between the conditioned and unconditioned stimuli was randomly chosen within 10–40 s (20 s on average). There was no intrinsic relationship between the times of occurrence of the conditioned stimulus and unconditioned stimuli stimulus events.

Figure 1 The training patterns of four traditional eyeblink conditioning groups. Based on whether the time of conditioned stimulus and unconditioned stimulus overlapped, eyeblink conditioning could be further divided into delay eyeblink conditioning and trace eyeblink conditioning. In delay eyeblink conditioning, (a) the conditioned stimulus happens prior to the unconditioned stimulus and ends with the unconditioned stimulus, whereas in trace eyeblink conditioning, (b–d) a time interval presents between the ending of the conditioned stimulus and the starting of the unconditioned stimulus.
Figure 1

The training patterns of four traditional eyeblink conditioning groups. Based on whether the time of conditioned stimulus and unconditioned stimulus overlapped, eyeblink conditioning could be further divided into delay eyeblink conditioning and trace eyeblink conditioning. In delay eyeblink conditioning, (a) the conditioned stimulus happens prior to the unconditioned stimulus and ends with the unconditioned stimulus, whereas in trace eyeblink conditioning, (b–d) a time interval presents between the ending of the conditioned stimulus and the starting of the unconditioned stimulus.

2.4 Data collection and recording

For neuronal stimulation by the electrode, the end of a frog heart clamp with a surgical suture was connected to a muscular-tension transducer (JZ100, Beijing, China), and the head was clipped to the free edge of the left upper eyelid of the guinea pigs, with the intensity maintained at a level that would allow the guinea pig to open the eyelid naturally. The movement could initiate tensional changes that could be transduced into an electric signal to record eyelid movements. Taking conditioned stimulus onset as the zero points, the baseline signal was taken from the average signal of 1 ms within 350 ms before conditioned stimulus onset. Blinks satisfying the following two conditions were determined as effective eyeblinks: (1) the upper eyelid movement was ≥baseline +1 mV; and (2) the total time was ≥15 ms. The analytical parameters were active eyeblinks within 200 ms before unconditioned stimulus onset and the magnitude of the difference between the maximum active eyeblinks within 200 ms before unconditioned stimulus onset eyeblink signal and the conditioned stimulus onset signal. The magnitude of the difference was based on the nictitating membrane response classical pathway [39].

2.5 Statistical analysis

Data were input into Microsoft Excel, and statistical analysis was performed using SPSS 18.0 (IBM, Armonk, NY, USA). Data were presented as means ± standard deviations. Graphs were plotted using Excel. Data were analyzed by the t-test and one-way ANOVA, and statistical significance was defined as P < 0.05.

3 Results

3.1 Successful eyeblink conditioning modeling using microcurrent pulse stimulation of the middle cerebellar peduncle

After behavior training, the site of electrode implantation was observed on slices. Based on our observation, a total of 28 guinea pigs had correct implantation at the left middle cerebellar peduncle (Figure 2a), out of which six belonged to the Delay group, five to the Trace-200ms group, six to the Trace-300ms group, five to the Trace-400ms group, and six to the control group. The two guinea pigs with incorrect electrode implantation were excluded from the statistical analysis. None of the animals had infections.

Figure 2 The location of implanted peduncle cerebellar medius-stimulating electrode and the variation pattern of CR-AR and the magnitude of the difference between the maximum active eyeblinks in trace eyeblink conditioning guinea pigs. (a) The red arrow points to the injured brain tissue after electrode implantation (magnification: 100×). (b and c) The line graph of CR-AR and the magnitude of the difference between the maximum active eyeblinks in different groups when constructing eyeblink conditioning models.
Figure 2

The location of implanted peduncle cerebellar medius-stimulating electrode and the variation pattern of CR-AR and the magnitude of the difference between the maximum active eyeblinks in trace eyeblink conditioning guinea pigs. (a) The red arrow points to the injured brain tissue after electrode implantation (magnification: 100×). (b and c) The line graph of CR-AR and the magnitude of the difference between the maximum active eyeblinks in different groups when constructing eyeblink conditioning models.

After 10 consecutive days of behavior training, the Delay, Trace-200ms, and Trace-300ms groups showed conditioned stimulus-associated active eyeblinks within 200 ms before unconditioned stimulus onset. On the 10th day of training, the CR-acquisition rate (AR) of all three groups was greater than 60%, indicating that the eyeblink conditioning model was established successfully. Furthermore, the CR-AR increased gradually with time. In the Trace-400ms group, however, the CR-AR on the 10th day of 2.50 ± 1.37% was not significantly different from that on the 1st day. Likewise, the control guinea pigs had a CR-AR of 1.66 ± 1.03% on the 10th day of training, which was not significantly different from that on the 1st day. Since there were no conditioned stimulus-associated active eyeblinks within 200 ms before unconditioned stimulus onset, the eyeblink conditioning model was, therefore, not established (Figure 2b). During the 10-day training, the magnitude of the difference between the maximum active eyeblinks of the Delay, Trace-200ms, and Trace-300ms groups increased gradually with time, and their values on the 10th day were significantly different from those on the 1st day. Nevertheless, the magnitude of the difference between the maximum active eyeblinks of the Trace-400ms group showed no significant difference between the 10th and 1st days, which again indicated that eyeblink conditioning was not established in these animals (Figure 2c). These results suggest that a microcurrent pulse could substitute the traditional sound and light as the conditioned stimulus to stimulate the middle cerebellar peduncle directly. In addition, using corneal blowing as the unconditioned stimulus, two types of conditioned reflex, namely delay eyeblink conditioning and trace eyeblink conditioning, could be established successfully with certain time intervals. It indicates that for time-associated events, the cerebellar cortex could independently complete the process of associative learning and memory.

According to our results, using specifically activated lateral pontine nucleus neurons and the projected middle cerebellar peduncle fibrous bundles as the conditioned stimulus, as well as an air puff to the left eyelid as the unconditioned stimulus, the trace eyeblink conditioning model with a conditioned stimulus-unconditioned stimulus time interval of 200 ms could be established successfully.

4 Discussion

As suggested by previous studies, during eyeblink conditioning, the cerebellar cortex receives signals from the mossy fiber and climbing fiber that are, respectively, activated by conditioned stimulus and unconditioned stimulus, and then, the signals are gathered and processed in the cerebellar cortex and deep nuclei, followed by appropriate active eyeblinks within 200 ms before unconditioned stimulus onset activity initiated by downstream motor circuits under the control of contralateral nucleus ruber and other nerves [29,51]. The delayed eyeblink conditioning only requires the participation of the cerebellum-brain stem circuit; therefore, the cerebellum could be directly excited without the involvement of the forebrain structures [52,53,54]. Studies of electrophysiology [29] and functional imaging [21,22] have also demonstrated that during delayed eyeblink conditioning, the cerebellar cortex is significantly activated in areas specific to motion and memory. Nevertheless, a study has suggested that in patients with cerebellar degeneration, eyeblink conditioning with a time interval of 1,000 ms could still be achieved [4]. Therefore, whether the cerebellar cortex can independently exert the function of temporal information processing is still controversial. In contrast to the models above, we used a microcurrent pulse to excite the input mossy fiber of the cerebellar cortex directly. It avoided the traditionally used forebrain–cerebellum circuit [2]. Gao et al. [55] showed that the cerebellar excitatory nucleocortical closed-loop circuitry relays premotor signals in a corollary discharge fashion. Therefore, our design excluded the influence of external factors as much as possible and facilitated the analysis of the cerebellum in terms of its independent role in associative learning and memory.

The presence of a time interval in the trace eyeblink conditioning model increased the difficulty of the cerebellar cortex to extract and process information based on the association between the conditioned and unconditioned stimuli. With unchanged conditioned stimulus and unconditioned stimulus, the establishment of the Trace model is harder than that of the Delay model; nevertheless, with an increasing time interval, the Trace model could be achieved with a lower CR-AR [56]. In this study, the Trace-200ms and Trace-300ms groups did not reach a CR-AR greater than 60% until the middle (6th day, 76.80 ± 6.76%) and late (9th day, 64.5 ± 7.00%) phases, but they still acquired trace eyeblink conditioning successfully. It indicates that when the time of occurrence of the conditioned and unconditioned stimuli does not overlap, the cerebellar cortex still establishes trace eyeblink conditioning independently, as suggested by a previous study [30]. The Albus–Marr Calculation Model suggests that when a conditioned stimulus-excited mossy fiber discharge does not overlap with the unconditioned stimulus-driven climbing fiber discharge, the ability of the cerebellum to establish trace eyeblink conditioning would be weakened in comparison to the condition of the overlapped conditioned and unconditioned stimuli. For trace eyeblink conditioning with a time interval ≥400 ms, additional input of nervous signal is needed to maintain the persistent excitation of mossy fiber, and thus, the time interval between climbing fiber could be compensated [57]. When the time interval was set at 400 ms, microcurrent pulse stimulation of the middle cerebellar peduncle failed to achieve trace eyeblink conditioning, and this is supported by the literature [30,55,56], as well as by Thompson and Steinmetz [2], Lee et al. [58], and Li et al. [59], who suggested that the cerebellum plays a role in the timing of associative learning and memory.

On the other hand, the studies by Kalmbach et al. [60,61,62] showed that when establishing a Delay/Trace double eyeblink conditioning, the achievement of trace eyeblink conditioning under a time interval >400 ms needs multistage forebrain impulse to mediate the process of learning and memorizing. Another study showed that patients with cerebellar degeneration could acquire trace eyeblink conditioning with a stimulation interval of 400 ms [4]. These results are different from our study’s, and some reasons might account for the differences. First, the animals used are rodents, whereas the above study used rabbits and even humans as their study subjects. Though the basic components of the cerebellar structures are similar, we cannot deny that the volume of the brain and the complexity of the brain structures among different species might cause some differences in the results [63,64]. Cats [65], rabbits [66], and mice [67] show conditioned responses at 400 ms. Our results will be validated in rabbits in future experiments. Second, Kalmbach et al. [60,61,62] used electric stimulation to the medial prefrontal cortex as the conditioned stimulus, and the excitation was conducted to the cerebellar cortex via the lateral pontine nucleus, whereas in our study, we directly stimulated the mossy fiber connected to the cerebellar cortex. Besides, the location of the microcurrent pulse excitation and the intensity of the microcurrent were also different. The intensity of the electric stimulation was only 20–80 μA, which is far lower than that used by Kalmbach et al. (200 mA). Indeed, large currents might cause peripheral sensory stimulation, which further triggers forebrain stimulation induced by other projection neurons and participate in the process of trace eyeblink conditioning as a compensatory signal.

Unfortunately, the present study was not designed to examine what occurs at the cellular level. Nevertheless, it is known that in cerebellar learning, the instruction signals for long-term depression (LTD) are from the climbing fiber along with the parallel fiber input [68]. The LTD plays a role in the output signal through the disinhibition of cerebellar nucleus neurons that receive GABAergic signals from Purkinje cells. A climbing fiber stimulus will elicit a voltage and calcium signal in Purkinje cells, promoting the induction of LTD [68]. Based on this model, we will analyze the number and morphology of dendritic spines in cerebellar Purkinje cells and granular cells and will also observe whether there is differential expression of mRNA, miRNA, lncRNA, and related proteins, thereby exploring possible downstream molecular targets. Ammann et al. [69] described that the motor cortex lead (in advance to the cerebellum) the generation of conditioned responses. Therefore, we will test in the future whether the electrical stimulation of the middle peduncle can backward activate the motor cortex circuits.

In conclusion, a microcurrent pulse stimulation was used to excite the lateral pontine nucleus-middle cerebellar peduncle circuit, thereby avoiding interference factors from either the external environment or other brain areas. It could be a good model for studying the function and molecular mechanism of the cerebellum during the establishment of eyeblink conditioning.

# These authors contributed equally to this work.

tel: +86-18302699558
tel: +86-18786777955

  1. Funding information: The study was supported by the Guizhou Science and Technology Agency (Guizhou Science and Technology Fund Project Qian Ke He J[2015]2090).

  2. Author contributions: All authors participated in the experiment design. Rui Li, Qi Li, Xiaolei Chu, Lan Li, Juan Li, Mingjing Xu, and Changlu Luo performed the experiments. All authors participated in data analysis and interpretation. Rui Li, Qi Li, Zhen Yang, Xiaoyi Li, and Kui Zhang wrote the manuscript with the participation of all authors. All authors approved the submitted version of the manuscript.

  3. Conflict of interest: Authors state no conflict of interest.

  4. Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

[1] Wikgren J, Nokia MS, Penttonen M. Hippocampo-cerebellar theta band phase synchrony in rabbits. Neuroscience. 2010 Feb 17;165(4):1538–45.10.1016/j.neuroscience.2009.11.044Search in Google Scholar PubMed

[2] Thompson RF, Steinmetz JE. The role of the cerebellum in classical conditioning of discrete behavioral responses. Neuroscience. 2009 Sep 1;162(3):732–55.10.1016/j.neuroscience.2009.01.041Search in Google Scholar PubMed

[3] Oristaglio J, Hyman West S, Ghaffari M, Lech MS, Verma BR, Harvey JA, et al. Children with autism spectrum disorders show abnormal conditioned response timing on delay, but not trace, eyeblink conditioning. Neuroscience. 2013 Sep 17;248:708–18.10.1016/j.neuroscience.2013.06.007Search in Google Scholar PubMed PubMed Central

[4] Gerwig M, Haerter K, Hajjar K, Dimitrova A, Maschke M, Kolb FP, et al. Trace eyeblink conditioning in human subjects with cerebellar lesions. Exp Brain Res. 2006 Mar;170(1):7–21.10.1007/s00221-005-0171-2Search in Google Scholar PubMed

[5] Gerwig M, Esser AC, Guberina H, Frings M, Kolb FP, Forsting M, et al. Trace eyeblink conditioning in patients with cerebellar degeneration: comparison of short and long trace intervals. Exp Brain Res. 2008 May;187(1):85–96.10.1007/s00221-008-1283-2Search in Google Scholar PubMed

[6] Gerwig M, Rauschen L, Gaul C, Katsarava Z, Timmann D. Subclinical cerebellar dysfunction in patients with migraine: evidence from eyeblink conditioning. Cephalalgia. 2014 Oct;34(11):904–13.10.1177/0333102414523844Search in Google Scholar PubMed

[7] Spottiswoode BS, Meintjes EM, Anderson AW, Molteno CD, Stanton ME, Dodge NC, et al. Diffusion tensor imaging of the cerebellum and eyeblink conditioning in fetal alcohol spectrum disorder. Alcohol Clin Exp Res. 2011 Dec;35(12):2174–83.10.1111/j.1530-0277.2011.01566.xSearch in Google Scholar PubMed PubMed Central

[8] Bolbecker AR, Petersen IT, Kent JS, Howell JM, O’Donnell BF, Hetrick WP. New insights into the nature of cerebellar-dependent eyeblink conditioning deficits in schizophrenia: a hierarchical linear modeling approach. Front Psychiatry. 2016;7:4.10.3389/fpsyt.2016.00004Search in Google Scholar PubMed PubMed Central

[9] Bolbecker AR, Kent JS, Petersen IT, Klaunig MJ, Forsyth JK, Howell JM, et al. Impaired cerebellar-dependent eyeblink conditioning in first-degree relatives of individuals with schizophrenia. Schizophr Bull. 2014 Sep;40(5):1001–10.10.1093/schbul/sbt112Search in Google Scholar PubMed PubMed Central

[10] Greer TL, Trivedi MH, Thompson LT. Impaired delay and trace eyeblink conditioning performance in major depressive disorder. J Affect Disord. 2005 Jun;86(2–3):235–45.10.1016/j.jad.2005.02.006Search in Google Scholar PubMed

[11] Antonietti A, Monaco J, D’Angelo E, Pedrocchi A, Casellato C. Dynamic redistribution of plasticity in a cerebellar spiking neural network reproducing an associative learning task perturbed by TMS. Int J Neural Syst. 2018 Nov;28(9):1850020.10.1142/S012906571850020XSearch in Google Scholar PubMed

[12] Steiner KM, Gisbertz Y, Chang DI, Koch B, Uslar E, Claassen J, et al. Extinction and renewal of conditioned eyeblink responses in focal cerebellar disease. Cerebellum. 2019 Apr;18(2):166–77.10.1007/s12311-018-0973-ySearch in Google Scholar PubMed

[13] Solbach K, Oostdam SJ, Kronenbuerger M, Timmann D, Gerwig M. Long trace eyeblink conditioning is largely preserved in essential tremor. Cerebellum. 2019 Feb;18(1):67–75.10.1007/s12311-018-0956-zSearch in Google Scholar PubMed

[14] Kloth AD, Badura A, Li A, Cherskov A, Connolly SG, Giovannucci A, et al. Cerebellar associative sensory learning defects in five mouse autism models. Elife. 2015 Jul 9;4:e06085.10.7554/eLife.06085Search in Google Scholar PubMed PubMed Central

[15] Piochon C, Kloth AD, Grasselli G, Titley HK, Nakayama H, Hashimoto K, et al. Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism. Nat Commun. 2014 Nov 24;5:5586.10.1038/ncomms6586Search in Google Scholar PubMed PubMed Central

[16] Paton JJ, Buonomano DV. The neural basis of timing: distributed mechanisms for diverse functions. Neuron. 2018 May 16;98(4):687–705.10.1016/j.neuron.2018.03.045Search in Google Scholar PubMed PubMed Central

[17] Bakhurin KI, Goudar V, Shobe JL, Claar LD, Buonomano DV, Masmanidis SC. Differential encoding of time by prefrontal and striatal network dynamics. J Neurosci. 2017 Jan 25;37(4):854–70.10.1523/JNEUROSCI.1789-16.2016Search in Google Scholar PubMed PubMed Central

[18] Zhang LQ, Yao J, Gao J, Sun L, Wang LT, Sui JF. Modulation of eyeblink conditioning through sensory processing of conditioned stimulus by cortical and subcortical regions. Behav Brain Res. 2019 Feb 1;359:149–55.10.1016/j.bbr.2018.10.035Search in Google Scholar PubMed

[19] Katschnig-Winter P, Schwingenschuh P, Davare M, Sadnicka A, Schmidt R, Rothwell JC, et al. Motor sequence learning and motor adaptation in primary cervical dystonia. J Clin Neurosci. 2014 Jun;21(6):934–8.10.1016/j.jocn.2013.08.019Search in Google Scholar PubMed

[20] Filip P, Lungu OV, Shaw DJ, Kasparek T, Bareš M. The mechanisms of movement control and time estimation in cervical dystonia patients. Neural Plast. 2013;2013:908741.10.1155/2013/908741Search in Google Scholar PubMed PubMed Central

[21] Cheng DT, Meintjes EM, Stanton ME, Desmond JE, Pienaar M, Dodge NC, et al. Functional MRI of cerebellar activity during eyeblink classical conditioning in children and adults. Hum Brain Mapp. 2014 Apr;35(4):1390–403.10.1002/hbm.22261Search in Google Scholar PubMed PubMed Central

[22] Thürling M, Kahl F, Maderwald S, Stefanescu RM, Schlamann M, Boele HJ, et al. Cerebellar cortex and cerebellar nuclei are concomitantly activated during eyeblink conditioning: a 7T fMRI study in humans. J Neurosci. 2015 Jan 21;35(3):1228–39.10.1523/JNEUROSCI.2492-14.2015Search in Google Scholar PubMed PubMed Central

[23] Harrington DL, Lee RR, Boyd LA, Rapcsak SZ, Knight RT. Does the representation of time depend on the cerebellum? Effect of cerebellar stroke. Brain. 2004 Mar;127(Pt 3):561–74.10.1093/brain/awh065Search in Google Scholar PubMed

[24] Spencer RMC, Ivry RB. Cerebellum and timing. In: Manto M, Schmahmann JD, Rossi F, Gruol DL, Koibuchi N, editors. Handbook of the cerebellum and cerebellar disorders. Dordrecht: Springer; 2013.10.1007/978-94-007-1333-8_52Search in Google Scholar

[25] Adamaszek M, D’Agata F, Ferrucci R, Habas C, Keulen S, Kirkby KC, et al. Consensus paper: cerebellum and emotion. Cerebellum. 2017 Apr;16(2):552–76.10.1007/s12311-016-0815-8Search in Google Scholar PubMed

[26] Meyer S, Kessner SS, Cheng B, Bönstrup M, Schulz R, Hummel FC, et al. Voxel-based lesion-symptom mapping of stroke lesions underlying somatosensory deficits. Neuroimage Clin. 2016;10:257–66.10.1016/j.nicl.2015.12.005Search in Google Scholar PubMed PubMed Central

[27] Weier K, Penner IK, Magon S, Amann M, Naegelin Y, Andelova M, et al. Cerebellar abnormalities contribute to disability including cognitive impairment in multiple sclerosis. PLoS One. 2014;9(1):e86916.10.1371/journal.pone.0086916Search in Google Scholar PubMed PubMed Central

[28] Kotani S, Kawahara S, Kirino Y. Trace eyeblink conditioning in decerebrate guinea pigs. Eur J Neurosci. 2003 Apr;17(7):1445–54.10.1046/j.1460-9568.2003.02566.xSearch in Google Scholar PubMed

[29] Svensson P, Jirenhed DA, Bengtsson F, Hesslow G. Effect of conditioned stimulus parameters on timing of conditioned Purkinje cell responses. J Neurophysiol. 2010 Mar;103(3):1329–36.10.1152/jn.00524.2009Search in Google Scholar PubMed

[30] Gould TJ, Steinmetz JE. Changes in rabbit cerebellar cortical and interpositus nucleus activity during acquisition, extinction, and backward classical eyelid conditioning. Neurobiol Learn Mem. 1996 Jan;65(1):17–34.10.1006/nlme.1996.0003Search in Google Scholar PubMed

[31] Monaco J, Rocchi L, Ginatempo F, D’Angelo E, Rothwell JC. Cerebellar Theta-Burst Stimulation Impairs Memory Consolidation in Eyeblink Classical Conditioning. Neural Plast. 2018;2018:6856475.10.1155/2018/6856475Search in Google Scholar

[32] Lavond DG, Kanzawa SA, Ivkovich D, Clark RE. Transfer of learning but not memory after unilateral cerebellar lesion in rabbits. Behav Neurosci. 1994 Apr;108(2):284–93.10.1037/0735-7044.108.2.284Search in Google Scholar

[33] Yeo CH. Cerebellum and classical conditioning of motor responses. Ann N Y Acad Sci. 1991;627:292–304.10.1111/j.1749-6632.1991.tb25933.xSearch in Google Scholar

[34] Yeo CH, Hardiman MJ. Cerebellar cortex and eyeblink conditioning: a reexamination. Exp Brain Res. 1992;88(3):623–38.10.1007/BF00228191Search in Google Scholar

[35] Yeo CH, Hardiman MJ, Glickstein M. Classical conditioning of the nictitating membrane response of the rabbit. IV. Lesions of the inferior olive. Exp Brain Res. 1986;63(1):81–92.10.1007/BF00235649Search in Google Scholar

[36] Yeo CH, Hardiman MJ, Glickstein M. Classical conditioning of the nictitating membrane response of the rabbit. II. Lesions of the cerebellar cortex. Exp Brain Res. 1985;60(1):99–113.10.1007/BF00237023Search in Google Scholar

[37] Yeo CH, Hardiman MJ, Glickstein M. Classical conditioning of the nictitating membrane response of the rabbit. I. Lesions of the cerebellar nuclei. Exp Brain Res. 1985;60(1):87–98.10.1007/BF00237022Search in Google Scholar

[38] Yeo CH, Hardiman MJ, Glickstein M. Classical conditioning of the nictitating membrane response of the rabbit. III. Connections of cerebellar lobule HVI. Exp Brain Res. 1985;60(1):114–26.10.1007/BF00237024Search in Google Scholar

[39] Yeo CH, Hardiman MJ, Moore JW, Russell IS. Trace conditioning of the nictitating membrane response in decorticate rabbits. Behav Brain Res. 1984 Jan;11(1):85–8.10.1016/0166-4328(84)90010-XSearch in Google Scholar

[40] Chen H, Yang L, Xu Y, Wu GY, Yao J, Zhang J, et al. Prefrontal control of cerebellum-dependent associative motor learning. Cerebellum. 2014 Feb;13(1):64–78.10.1007/s12311-013-0517-4Search in Google Scholar PubMed

[41] Weymar M, Keil A, Hamm AO. Timing the fearful brain: unspecific hypervigilance and spatial attention in early visual perception. Soc Cogn Affect Neurosci. 2014 May;9(5):723–9.10.1093/scan/nst044Search in Google Scholar PubMed PubMed Central

[42] Schara U, Busse M, Timmann D, Gerwig M. Cerebellar-dependent associative learning is preserved in Duchenne muscular dystrophy: a study using delay eyeblink conditioning. PLoS One. 2015;10(5):e0126528.10.1371/journal.pone.0126528Search in Google Scholar

[43] Siegel JJ. Prefrontal single-neuron responses after changes in task contingencies during trace eyeblink conditioning in rabbits. eNeuro. 2016 Jul 18;3(4):ENEURO.0057–16.2016.10.1523/ENEURO.0057-16.2016Search in Google Scholar

[44] Liu S, Lin S, Wu G, Sui J, Cao W. Histological features and channel functions of adeno-associated virus AAV2/8-CaMKIIα-ChR2-mCherry in glutamatergic neurons. Chongqing, China: Journal of Third Military Medical University, 2015.Search in Google Scholar

[45] Tracy JA, Thompson JK, Krupa DJ, Thompson RF. Evidence of plasticity in the pontocerebellar conditioned stimulus pathway during classical conditioning of the eyeblink response in the rabbit. Behav Neurosci. 2013 Oct;127(5):676–89.10.1037/a0033979Search in Google Scholar

[46] Halverson HE, Freeman JH. Medial auditory thalamic input to the lateral pontine nuclei is necessary for auditory eyeblink conditioning. Neurobiol Learn Mem. 2010 Jan;93(1):92–8.10.1016/j.nlm.2009.08.008Search in Google Scholar

[47] Wu GY, Yao J, Fan ZL, Zhang LQ, Li X, Zhao CD, et al. Classical eyeblink conditioning using electrical stimulation of caudal mPFC as conditioned stimulus is dependent on cerebellar interpositus nucleus in guinea pigs. Acta Pharmacol Sin. 2012 Jun;33(6):717–27.10.1038/aps.2012.32Search in Google Scholar

[48] Yao J, Wu GY, Liu GL, Liu SL, Yang Y, Wu B, et al. Transfer of classical eyeblink conditioning with electrical stimulation of mPFC or tone as conditioned stimulus in guinea pigs. Behav Brain Res. 2014 Nov 1;274:19–29.10.1016/j.bbr.2014.07.051Search in Google Scholar

[49] Steinmetz JE, Rosen DJ, Chapman PF, Lavond DG, Thompson RF. Classical conditioning of the rabbit eyelid response with a mossy-fiber stimulation CS: I. Pontine nuclei and middle cerebellar peduncle stimulation. Behav Neurosci. 1986 Dec;100(6):878–87.10.1037/0735-7044.100.6.878Search in Google Scholar

[50] Shinkman PG, Swain RA, Thompson RF. Classical conditioning with electrical stimulation of cerebellum as both conditioned and unconditioned stimulus. Behav Neurosci. 1996 Oct;110(5):914–21.10.1037/0735-7044.110.5.914Search in Google Scholar

[51] Hesslow G, Svensson P, Ivarsson M. Learned movements elicited by direct stimulation of cerebellar mossy fiber afferents. Neuron. 1999 Sep;24(1):179–85.10.1016/S0896-6273(00)80831-4Search in Google Scholar

[52] Yang Y, Lei C, Feng H, Sui JF. The neural circuitry and molecular mechanisms underlying delay and trace eyeblink conditioning in mice. Behav Brain Res. 2015 Feb 1;278:307–14.10.1016/j.bbr.2014.10.006Search in Google Scholar PubMed

[53] Wu GY, Yao J, Zhang LQ, Li X, Fan ZL, Yang Y, et al. Reevaluating the role of the medial prefrontal cortex in delay eyeblink conditioning. Neurobiol Learn Mem. 2012 Mar;97(3):277–88.10.1016/j.nlm.2012.02.001Search in Google Scholar PubMed

[54] Takehara-Nishiuchi K. The anatomy and physiology of eyeblink classical conditioning. Curr Top Behav Neurosci. 2018;37:297–323.10.1007/7854_2016_455Search in Google Scholar PubMed

[55] Gao Z, Proietti-Onori M, Lin Z, Ten Brinke MM, Boele HJ, Potters JW, et al. Excitatory cerebellar nucleocortical circuit provides internal amplification during associative conditioning. Neuron. 2016 Feb 3;89(3):645–57.10.1016/j.neuron.2016.01.008Search in Google Scholar PubMed PubMed Central

[56] Waring JD, Seiger AN, Solomon PR, Budson AE, Kensinger EA. Memory for the 2008 presidential election in healthy ageing and mild cognitive impairment. Cogn Emot. 2014;28(8):1407–21.10.1080/02699931.2014.886558Search in Google Scholar PubMed PubMed Central

[57] Woodruff-Pak DS, Green JT, Levin SI, Meisler MH. Inactivation of sodium channel Scn8A (Na-sub(v)1.6) in Purkinje neurons impairs learning in Morris water maze and delay but not trace eyeblink classical conditioning. Behav Neurosci. 2006 Apr;120(2):229–40.10.1037/0735-7044.120.2.229Search in Google Scholar PubMed

[58] Lee KH, Mathews PJ, Reeves AM, Choe KY, Jami SA, Serrano RE, et al. Circuit mechanisms underlying motor memory formation in the cerebellum. Neuron. 2015 Apr 22;86(2):529–40.10.1016/j.neuron.2015.03.010Search in Google Scholar PubMed PubMed Central

[59] Li DB, Yao J, Sun L, Wu B, Li X, Liu SL, et al. Reevaluating the ability of cerebellum in associative motor learning. Sci Rep. 2019 Apr 15;9(1):6029.10.1038/s41598-019-42413-5Search in Google Scholar PubMed PubMed Central

[60] Kalmbach BE, Ohyama T, Kreider JC, Riusech F, Mauk MD. Interactions between prefrontal cortex and cerebellum revealed by trace eyelid conditioning. Learn Mem. 2009 Jan;16(1):86–95.10.1101/lm.1178309Search in Google Scholar PubMed PubMed Central

[61] Kalmbach BE, Voicu H, Ohyama T, Mauk MD. A subtraction mechanism of temporal coding in cerebellar cortex. J Neurosci. 2011 Feb 9;31(6):2025–34.10.1523/JNEUROSCI.4212-10.2011Search in Google Scholar PubMed PubMed Central

[62] Kalmbach BE, Davis T, Ohyama T, Riusech F, Nores WL, Mauk MD. Cerebellar cortex contributions to the expression and timing of conditioned eyelid responses. J Neurophysiol. 2010 Apr;103(4):2039–49.10.1152/jn.00033.2010Search in Google Scholar PubMed PubMed Central

[63] Hofman MA. Evolution of the human brain: when bigger is better. Front Neuroanat. 2014;8:15.10.3389/fnana.2014.00015Search in Google Scholar PubMed PubMed Central

[64] Roth G. Convergent evolution of complex brains and high intelligence. Philos Trans R Soc Lond B Biol Sci. 2015 Dec 19;370(1684). https://doi.org/10.1098/rstb.2015.0049.10.1098/rstb.2015.0049Search in Google Scholar PubMed PubMed Central

[65] Gruart A, Yeo CH. Cerebellar cortex and eyeblink conditioning: bilateral regulation of conditioned responses. Exp Brain Res. 1995;104(3):431–48.10.1007/BF00231978Search in Google Scholar PubMed

[66] Caro-Martín CR, Leal-Campanario R, Sánchez-Campusano R, Delgado-García JM, Gruart A. A variable oscillator underlies the measurement of time intervals in the rostral medial prefrontal cortex during classical eyeblink conditioning in rabbits. J Neurosci. 2015 Nov 4;35(44):14809–21.10.1523/JNEUROSCI.2285-15.2015Search in Google Scholar PubMed PubMed Central

[67] Gruart A, Muñoz MD, Delgado-García JM. Involvement of the CA3-CA1 synapse in the acquisition of associative learning in behaving mice. J Neurosci. 2006 Jan 25;26(4):1077–87.10.1523/JNEUROSCI.2834-05.2006Search in Google Scholar PubMed PubMed Central

[68] Titley HK, Kislin M, Simmons DH, Wang SS, Hansel C. Complex spike clusters and false-positive rejection in a cerebellar supervised learning rule. J Physiol. 2019 Aug;597(16):4387–406.10.1113/JP278502Search in Google Scholar PubMed PubMed Central

[69] Ammann C, Márquez-Ruiz J, Gómez-Climent M, Delgado-García JM, Gruart A. The motor cortex is involved in the generation of classically conditioned eyelid responses in behaving rabbits. J Neurosci. 2016 Jun 29;36(26):6988–7001.10.1523/JNEUROSCI.4190-15.2016Search in Google Scholar PubMed PubMed Central

Received: 2021-09-26
Revised: 2022-06-23
Accepted: 2022-06-24
Published Online: 2022-09-14

© 2022 Rui Li et al., published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Articles in the same Issue

  1. Biomedical Sciences
  2. Effects of direct oral anticoagulants dabigatran and rivaroxaban on the blood coagulation function in rabbits
  3. The mother of all battles: Viruses vs humans. Can humans avoid extinction in 50–100 years?
  4. Knockdown of G1P3 inhibits cell proliferation and enhances the cytotoxicity of dexamethasone in acute lymphoblastic leukemia
  5. LINC00665 regulates hepatocellular carcinoma by modulating mRNA via the m6A enzyme
  6. Association study of CLDN14 variations in patients with kidney stones
  7. Concanavalin A-induced autoimmune hepatitis model in mice: Mechanisms and future outlook
  8. Regulation of miR-30b in cancer development, apoptosis, and drug resistance
  9. Informatic analysis of the pulmonary microecology in non-cystic fibrosis bronchiectasis at three different stages
  10. Swimming attenuates tumor growth in CT-26 tumor-bearing mice and suppresses angiogenesis by mediating the HIF-1α/VEGFA pathway
  11. Characterization of intestinal microbiota and serum metabolites in patients with mild hepatic encephalopathy
  12. Functional conservation and divergence in plant-specific GRF gene family revealed by sequences and expression analysis
  13. Application of the FLP/LoxP-FRT recombination system to switch the eGFP expression in a model prokaryote
  14. Biomedical evaluation of antioxidant properties of lamb meat enriched with iodine and selenium
  15. Intravenous infusion of the exosomes derived from human umbilical cord mesenchymal stem cells enhance neurological recovery after traumatic brain injury via suppressing the NF-κB pathway
  16. Effect of dietary pattern on pregnant women with gestational diabetes mellitus and its clinical significance
  17. Potential regulatory mechanism of TNF-α/TNFR1/ANXA1 in glioma cells and its role in glioma cell proliferation
  18. Effect of the genetic mutant G71R in uridine diphosphate-glucuronosyltransferase 1A1 on the conjugation of bilirubin
  19. Quercetin inhibits cytotoxicity of PC12 cells induced by amyloid-beta 25–35 via stimulating estrogen receptor α, activating ERK1/2, and inhibiting apoptosis
  20. Nutrition intervention in the management of novel coronavirus pneumonia patients
  21. circ-CFH promotes the development of HCC by regulating cell proliferation, apoptosis, migration, invasion, and glycolysis through the miR-377-3p/RNF38 axis
  22. Bmi-1 directly upregulates glucose transporter 1 in human gastric adenocarcinoma
  23. Lacunar infarction aggravates the cognitive deficit in the elderly with white matter lesion
  24. Hydroxysafflor yellow A improved retinopathy via Nrf2/HO-1 pathway in rats
  25. Comparison of axon extension: PTFE versus PLA formed by a 3D printer
  26. Elevated IL-35 level and iTr35 subset increase the bacterial burden and lung lesions in Mycobacterium tuberculosis-infected mice
  27. A case report of CAT gene and HNF1β gene variations in a patient with early-onset diabetes
  28. Study on the mechanism of inhibiting patulin production by fengycin
  29. SOX4 promotes high-glucose-induced inflammation and angiogenesis of retinal endothelial cells by activating NF-κB signaling pathway
  30. Relationship between blood clots and COVID-19 vaccines: A literature review
  31. Analysis of genetic characteristics of 436 children with dysplasia and detailed analysis of rare karyotype
  32. Bioinformatics network analyses of growth differentiation factor 11
  33. NR4A1 inhibits the epithelial–mesenchymal transition of hepatic stellate cells: Involvement of TGF-β–Smad2/3/4–ZEB signaling
  34. Expression of Zeb1 in the differentiation of mouse embryonic stem cell
  35. Study on the genetic damage caused by cadmium sulfide quantum dots in human lymphocytes
  36. Association between single-nucleotide polymorphisms of NKX2.5 and congenital heart disease in Chinese population: A meta-analysis
  37. Assessment of the anesthetic effect of modified pentothal sodium solution on Sprague-Dawley rats
  38. Genetic susceptibility to high myopia in Han Chinese population
  39. Potential biomarkers and molecular mechanisms in preeclampsia progression
  40. Silencing circular RNA-friend leukemia virus integration 1 restrained malignancy of CC cells and oxaliplatin resistance by disturbing dyskeratosis congenita 1
  41. Endostar plus pembrolizumab combined with a platinum-based dual chemotherapy regime for advanced pulmonary large-cell neuroendocrine carcinoma as a first-line treatment: A case report
  42. The significance of PAK4 in signaling and clinicopathology: A review
  43. Sorafenib inhibits ovarian cancer cell proliferation and mobility and induces radiosensitivity by targeting the tumor cell epithelial–mesenchymal transition
  44. Characterization of rabbit polyclonal antibody against camel recombinant nanobodies
  45. Active legumain promotes invasion and migration of neuroblastoma by regulating epithelial-mesenchymal transition
  46. Effect of cell receptors in the pathogenesis of osteoarthritis: Current insights
  47. MT-12 inhibits the proliferation of bladder cells in vitro and in vivo by enhancing autophagy through mitochondrial dysfunction
  48. Study of hsa_circRNA_000121 and hsa_circRNA_004183 in papillary thyroid microcarcinoma
  49. BuyangHuanwu Decoction attenuates cerebral vasospasm caused by subarachnoid hemorrhage in rats via PI3K/AKT/eNOS axis
  50. Effects of the interaction of Notch and TLR4 pathways on inflammation and heart function in septic heart
  51. Monosodium iodoacetate-induced subchondral bone microstructure and inflammatory changes in an animal model of osteoarthritis
  52. A rare presentation of type II Abernethy malformation and nephrotic syndrome: Case report and review
  53. Rapid death due to pulmonary epithelioid haemangioendothelioma in several weeks: A case report
  54. Hepatoprotective role of peroxisome proliferator-activated receptor-α in non-cancerous hepatic tissues following transcatheter arterial embolization
  55. Correlation between peripheral blood lymphocyte subpopulations and primary systemic lupus erythematosus
  56. A novel SLC8A1-ALK fusion in lung adenocarcinoma confers sensitivity to alectinib: A case report
  57. β-Hydroxybutyrate upregulates FGF21 expression through inhibition of histone deacetylases in hepatocytes
  58. Identification of metabolic genes for the prediction of prognosis and tumor microenvironment infiltration in early-stage non-small cell lung cancer
  59. BTBD10 inhibits glioma tumorigenesis by downregulating cyclin D1 and p-Akt
  60. Mucormycosis co-infection in COVID-19 patients: An update
  61. Metagenomic next-generation sequencing in diagnosing Pneumocystis jirovecii pneumonia: A case report
  62. Long non-coding RNA HOXB-AS1 is a prognostic marker and promotes hepatocellular carcinoma cells’ proliferation and invasion
  63. Preparation and evaluation of LA-PEG-SPION, a targeted MRI contrast agent for liver cancer
  64. Proteomic analysis of the liver regulating lipid metabolism in Chaohu ducks using two-dimensional electrophoresis
  65. Nasopharyngeal tuberculosis: A case report
  66. Characterization and evaluation of anti-Salmonella enteritidis activity of indigenous probiotic lactobacilli in mice
  67. Aberrant pulmonary immune response of obese mice to periodontal infection
  68. Bacteriospermia – A formidable player in male subfertility
  69. In silico and in vivo analysis of TIPE1 expression in diffuse large B cell lymphoma
  70. Effects of KCa channels on biological behavior of trophoblasts
  71. Interleukin-17A influences the vulnerability rather than the size of established atherosclerotic plaques in apolipoprotein E-deficient mice
  72. Multiple organ failure and death caused by Staphylococcus aureus hip infection: A case report
  73. Prognostic signature related to the immune environment of oral squamous cell carcinoma
  74. Primary and metastatic squamous cell carcinoma of the thyroid gland: Two case reports
  75. Neuroprotective effects of crocin and crocin-loaded niosomes against the paraquat-induced oxidative brain damage in rats
  76. Role of MMP-2 and CD147 in kidney fibrosis
  77. Geometric basis of action potential of skeletal muscle cells and neurons
  78. Babesia microti-induced fulminant sepsis in an immunocompromised host: A case report and the case-specific literature review
  79. Role of cerebellar cortex in associative learning and memory in guinea pigs
  80. Application of metagenomic next-generation sequencing technique for diagnosing a specific case of necrotizing meningoencephalitis caused by human herpesvirus 2
  81. Case report: Quadruple primary malignant neoplasms including esophageal, ureteral, and lung in an elderly male
  82. Long non-coding RNA NEAT1 promotes angiogenesis in hepatoma carcinoma via the miR-125a-5p/VEGF pathway
  83. Osteogenic differentiation of periodontal membrane stem cells in inflammatory environments
  84. Knockdown of SHMT2 enhances the sensitivity of gastric cancer cells to radiotherapy through the Wnt/β-catenin pathway
  85. Continuous renal replacement therapy combined with double filtration plasmapheresis in the treatment of severe lupus complicated by serious bacterial infections in children: A case report
  86. Simultaneous triple primary malignancies, including bladder cancer, lymphoma, and lung cancer, in an elderly male: A case report
  87. Preclinical immunogenicity assessment of a cell-based inactivated whole-virion H5N1 influenza vaccine
  88. One case of iodine-125 therapy – A new minimally invasive treatment of intrahepatic cholangiocarcinoma
  89. S1P promotes corneal trigeminal neuron differentiation and corneal nerve repair via upregulating nerve growth factor expression in a mouse model
  90. Early cancer detection by a targeted methylation assay of circulating tumor DNA in plasma
  91. Calcifying nanoparticles initiate the calcification process of mesenchymal stem cells in vitro through the activation of the TGF-β1/Smad signaling pathway and promote the decay of echinococcosis
  92. Evaluation of prognostic markers in patients infected with SARS-CoV-2
  93. N6-Methyladenosine-related alternative splicing events play a role in bladder cancer
  94. Characterization of the structural, oxidative, and immunological features of testis tissue from Zucker diabetic fatty rats
  95. Effects of glucose and osmotic pressure on the proliferation and cell cycle of human chorionic trophoblast cells
  96. Investigation of genotype diversity of 7,804 norovirus sequences in humans and animals of China
  97. Characteristics and karyotype analysis of a patient with turner syndrome complicated with multiple-site tumors: A case report
  98. Aggravated renal fibrosis is positively associated with the activation of HMGB1-TLR2/4 signaling in STZ-induced diabetic mice
  99. Distribution characteristics of SARS-CoV-2 IgM/IgG in false-positive results detected by chemiluminescent immunoassay
  100. SRPX2 attenuated oxygen–glucose deprivation and reperfusion-induced injury in cardiomyocytes via alleviating endoplasmic reticulum stress-induced apoptosis through targeting PI3K/Akt/mTOR axis
  101. Aquaporin-8 overexpression is involved in vascular structure and function changes in placentas of gestational diabetes mellitus patients
  102. Relationship between CRP gene polymorphisms and ischemic stroke risk: A systematic review and meta-analysis
  103. Effects of growth hormone on lipid metabolism and sexual development in pubertal obese male rats
  104. Cloning and identification of the CTLA-4IgV gene and functional application of vaccine in Xinjiang sheep
  105. Antitumor activity of RUNX3: Upregulation of E-cadherin and downregulation of the epithelial–mesenchymal transition in clear-cell renal cell carcinoma
  106. PHF8 promotes osteogenic differentiation of BMSCs in old rat with osteoporosis by regulating Wnt/β-catenin pathway
  107. A review of the current state of the computer-aided diagnosis (CAD) systems for breast cancer diagnosis
  108. Bilateral dacryoadenitis in adult-onset Still’s disease: A case report
  109. A novel association between Bmi-1 protein expression and the SUVmax obtained by 18F-FDG PET/CT in patients with gastric adenocarcinoma
  110. The role of erythrocytes and erythroid progenitor cells in tumors
  111. Relationship between platelet activation markers and spontaneous abortion: A meta-analysis
  112. Abnormal methylation caused by folic acid deficiency in neural tube defects
  113. Silencing TLR4 using an ultrasound-targeted microbubble destruction-based shRNA system reduces ischemia-induced seizures in hyperglycemic rats
  114. Plant Sciences
  115. Seasonal succession of bacterial communities in cultured Caulerpa lentillifera detected by high-throughput sequencing
  116. Cloning and prokaryotic expression of WRKY48 from Caragana intermedia
  117. Novel Brassica hybrids with different resistance to Leptosphaeria maculans reveal unbalanced rDNA signal patterns
  118. Application of exogenous auxin and gibberellin regulates the bolting of lettuce (Lactuca sativa L.)
  119. Phytoremediation of pollutants from wastewater: A concise review
  120. Genome-wide identification and characterization of NBS-encoding genes in the sweet potato wild ancestor Ipomoea trifida (H.B.K.)
  121. Alleviative effects of magnetic Fe3O4 nanoparticles on the physiological toxicity of 3-nitrophenol to rice (Oryza sativa L.) seedlings
  122. Selection and functional identification of Dof genes expressed in response to nitrogen in Populus simonii × Populus nigra
  123. Study on pecan seed germination influenced by seed endocarp
  124. Identification of active compounds in Ophiopogonis Radix from different geographical origins by UPLC-Q/TOF-MS combined with GC-MS approaches
  125. The entire chloroplast genome sequence of Asparagus cochinchinensis and genetic comparison to Asparagus species
  126. Genome-wide identification of MAPK family genes and their response to abiotic stresses in tea plant (Camellia sinensis)
  127. Selection and validation of reference genes for RT-qPCR analysis of different organs at various development stages in Caragana intermedia
  128. Cloning and expression analysis of SERK1 gene in Diospyros lotus
  129. Integrated metabolomic and transcriptomic profiling revealed coping mechanisms of the edible and medicinal homologous plant Plantago asiatica L. cadmium resistance
  130. A missense variant in NCF1 is associated with susceptibility to unexplained recurrent spontaneous abortion
  131. Assessment of drought tolerance indices in faba bean genotypes under different irrigation regimes
  132. The entire chloroplast genome sequence of Asparagus setaceus (Kunth) Jessop: Genome structure, gene composition, and phylogenetic analysis in Asparagaceae
  133. Food Science
  134. Dietary food additive monosodium glutamate with or without high-lipid diet induces spleen anomaly: A mechanistic approach on rat model
  135. Binge eating disorder during COVID-19
  136. Potential of honey against the onset of autoimmune diabetes and its associated nephropathy, pancreatitis, and retinopathy in type 1 diabetic animal model
  137. FTO gene expression in diet-induced obesity is downregulated by Solanum fruit supplementation
  138. Physical activity enhances fecal lactobacilli in rats chronically drinking sweetened cola beverage
  139. Supercritical CO2 extraction, chemical composition, and antioxidant effects of Coreopsis tinctoria Nutt. oleoresin
  140. Functional constituents of plant-based foods boost immunity against acute and chronic disorders
  141. Effect of selenium and methods of protein extraction on the proteomic profile of Saccharomyces yeast
  142. Microbial diversity of milk ghee in southern Gansu and its effect on the formation of ghee flavor compounds
  143. Ecology and Environmental Sciences
  144. Effects of heavy metals on bacterial community surrounding Bijiashan mining area located in northwest China
  145. Microorganism community composition analysis coupling with 15N tracer experiments reveals the nitrification rate and N2O emissions in low pH soils in Southern China
  146. Genetic diversity and population structure of Cinnamomum balansae Lecomte inferred by microsatellites
  147. Preliminary screening of microplastic contamination in different marine fish species of Taif market, Saudi Arabia
  148. Plant volatile organic compounds attractive to Lygus pratensis
  149. Effects of organic materials on soil bacterial community structure in long-term continuous cropping of tomato in greenhouse
  150. Effects of soil treated fungicide fluopimomide on tomato (Solanum lycopersicum L.) disease control and plant growth
  151. Prevalence of Yersinia pestis among rodents captured in a semi-arid tropical ecosystem of south-western Zimbabwe
  152. Effects of irrigation and nitrogen fertilization on mitigating salt-induced Na+ toxicity and sustaining sea rice growth
  153. Bioengineering and Biotechnology
  154. Poly-l-lysine-caused cell adhesion induces pyroptosis in THP-1 monocytes
  155. Development of alkaline phosphatase-scFv and its use for one-step enzyme-linked immunosorbent assay for His-tagged protein detection
  156. Development and validation of a predictive model for immune-related genes in patients with tongue squamous cell carcinoma
  157. Agriculture
  158. Effects of chemical-based fertilizer replacement with biochar-based fertilizer on albic soil nutrient content and maize yield
  159. Genome-wide identification and expression analysis of CPP-like gene family in Triticum aestivum L. under different hormone and stress conditions
  160. Agronomic and economic performance of mung bean (Vigna radiata L.) varieties in response to rates of blended NPS fertilizer in Kindo Koysha district, Southern Ethiopia
  161. Influence of furrow irrigation regime on the yield and water consumption indicators of winter wheat based on a multi-level fuzzy comprehensive evaluation
  162. Discovery of exercise-related genes and pathway analysis based on comparative genomes of Mongolian originated Abaga and Wushen horse
  163. Lessons from integrated seasonal forecast-crop modelling in Africa: A systematic review
  164. Evolution trend of soil fertility in tobacco-planting area of Chenzhou, Hunan Province, China
  165. Animal Sciences
  166. Morphological and molecular characterization of Tatera indica Hardwicke 1807 (Rodentia: Muridae) from Pothwar, Pakistan
  167. Research on meat quality of Qianhua Mutton Merino sheep and Small-tail Han sheep
  168. SI: A Scientific Memoir
  169. Suggestions on leading an academic research laboratory group
  170. My scientific genealogy and the Toronto ACDC Laboratory, 1988–2022
  171. Erratum
  172. Erratum to “Changes of immune cells in patients with hepatocellular carcinoma treated by radiofrequency ablation and hepatectomy, a pilot study”
  173. Erratum to “A two-microRNA signature predicts the progression of male thyroid cancer”
  174. Retraction
  175. Retraction of “Lidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis”
https://doi.org/10.1515/biol-2022-0471
Keywords for this article
cerebellar cortex; delay eyeblink conditioning; lateral pontine nuclei; middle cerebellar peduncle; trace eyeblink conditioning
Creative Commons
BY 4.0

Articles in the same Issue

  1. Biomedical Sciences
  2. Effects of direct oral anticoagulants dabigatran and rivaroxaban on the blood coagulation function in rabbits
  3. The mother of all battles: Viruses vs humans. Can humans avoid extinction in 50–100 years?
  4. Knockdown of G1P3 inhibits cell proliferation and enhances the cytotoxicity of dexamethasone in acute lymphoblastic leukemia
  5. LINC00665 regulates hepatocellular carcinoma by modulating mRNA via the m6A enzyme
  6. Association study of CLDN14 variations in patients with kidney stones
  7. Concanavalin A-induced autoimmune hepatitis model in mice: Mechanisms and future outlook
  8. Regulation of miR-30b in cancer development, apoptosis, and drug resistance
  9. Informatic analysis of the pulmonary microecology in non-cystic fibrosis bronchiectasis at three different stages
  10. Swimming attenuates tumor growth in CT-26 tumor-bearing mice and suppresses angiogenesis by mediating the HIF-1α/VEGFA pathway
  11. Characterization of intestinal microbiota and serum metabolites in patients with mild hepatic encephalopathy
  12. Functional conservation and divergence in plant-specific GRF gene family revealed by sequences and expression analysis
  13. Application of the FLP/LoxP-FRT recombination system to switch the eGFP expression in a model prokaryote
  14. Biomedical evaluation of antioxidant properties of lamb meat enriched with iodine and selenium
  15. Intravenous infusion of the exosomes derived from human umbilical cord mesenchymal stem cells enhance neurological recovery after traumatic brain injury via suppressing the NF-κB pathway
  16. Effect of dietary pattern on pregnant women with gestational diabetes mellitus and its clinical significance
  17. Potential regulatory mechanism of TNF-α/TNFR1/ANXA1 in glioma cells and its role in glioma cell proliferation
  18. Effect of the genetic mutant G71R in uridine diphosphate-glucuronosyltransferase 1A1 on the conjugation of bilirubin
  19. Quercetin inhibits cytotoxicity of PC12 cells induced by amyloid-beta 25–35 via stimulating estrogen receptor α, activating ERK1/2, and inhibiting apoptosis
  20. Nutrition intervention in the management of novel coronavirus pneumonia patients
  21. circ-CFH promotes the development of HCC by regulating cell proliferation, apoptosis, migration, invasion, and glycolysis through the miR-377-3p/RNF38 axis
  22. Bmi-1 directly upregulates glucose transporter 1 in human gastric adenocarcinoma
  23. Lacunar infarction aggravates the cognitive deficit in the elderly with white matter lesion
  24. Hydroxysafflor yellow A improved retinopathy via Nrf2/HO-1 pathway in rats
  25. Comparison of axon extension: PTFE versus PLA formed by a 3D printer
  26. Elevated IL-35 level and iTr35 subset increase the bacterial burden and lung lesions in Mycobacterium tuberculosis-infected mice
  27. A case report of CAT gene and HNF1β gene variations in a patient with early-onset diabetes
  28. Study on the mechanism of inhibiting patulin production by fengycin
  29. SOX4 promotes high-glucose-induced inflammation and angiogenesis of retinal endothelial cells by activating NF-κB signaling pathway
  30. Relationship between blood clots and COVID-19 vaccines: A literature review
  31. Analysis of genetic characteristics of 436 children with dysplasia and detailed analysis of rare karyotype
  32. Bioinformatics network analyses of growth differentiation factor 11
  33. NR4A1 inhibits the epithelial–mesenchymal transition of hepatic stellate cells: Involvement of TGF-β–Smad2/3/4–ZEB signaling
  34. Expression of Zeb1 in the differentiation of mouse embryonic stem cell
  35. Study on the genetic damage caused by cadmium sulfide quantum dots in human lymphocytes
  36. Association between single-nucleotide polymorphisms of NKX2.5 and congenital heart disease in Chinese population: A meta-analysis
  37. Assessment of the anesthetic effect of modified pentothal sodium solution on Sprague-Dawley rats
  38. Genetic susceptibility to high myopia in Han Chinese population
  39. Potential biomarkers and molecular mechanisms in preeclampsia progression
  40. Silencing circular RNA-friend leukemia virus integration 1 restrained malignancy of CC cells and oxaliplatin resistance by disturbing dyskeratosis congenita 1
  41. Endostar plus pembrolizumab combined with a platinum-based dual chemotherapy regime for advanced pulmonary large-cell neuroendocrine carcinoma as a first-line treatment: A case report
  42. The significance of PAK4 in signaling and clinicopathology: A review
  43. Sorafenib inhibits ovarian cancer cell proliferation and mobility and induces radiosensitivity by targeting the tumor cell epithelial–mesenchymal transition
  44. Characterization of rabbit polyclonal antibody against camel recombinant nanobodies
  45. Active legumain promotes invasion and migration of neuroblastoma by regulating epithelial-mesenchymal transition
  46. Effect of cell receptors in the pathogenesis of osteoarthritis: Current insights
  47. MT-12 inhibits the proliferation of bladder cells in vitro and in vivo by enhancing autophagy through mitochondrial dysfunction
  48. Study of hsa_circRNA_000121 and hsa_circRNA_004183 in papillary thyroid microcarcinoma
  49. BuyangHuanwu Decoction attenuates cerebral vasospasm caused by subarachnoid hemorrhage in rats via PI3K/AKT/eNOS axis
  50. Effects of the interaction of Notch and TLR4 pathways on inflammation and heart function in septic heart
  51. Monosodium iodoacetate-induced subchondral bone microstructure and inflammatory changes in an animal model of osteoarthritis
  52. A rare presentation of type II Abernethy malformation and nephrotic syndrome: Case report and review
  53. Rapid death due to pulmonary epithelioid haemangioendothelioma in several weeks: A case report
  54. Hepatoprotective role of peroxisome proliferator-activated receptor-α in non-cancerous hepatic tissues following transcatheter arterial embolization
  55. Correlation between peripheral blood lymphocyte subpopulations and primary systemic lupus erythematosus
  56. A novel SLC8A1-ALK fusion in lung adenocarcinoma confers sensitivity to alectinib: A case report
  57. β-Hydroxybutyrate upregulates FGF21 expression through inhibition of histone deacetylases in hepatocytes
  58. Identification of metabolic genes for the prediction of prognosis and tumor microenvironment infiltration in early-stage non-small cell lung cancer
  59. BTBD10 inhibits glioma tumorigenesis by downregulating cyclin D1 and p-Akt
  60. Mucormycosis co-infection in COVID-19 patients: An update
  61. Metagenomic next-generation sequencing in diagnosing Pneumocystis jirovecii pneumonia: A case report
  62. Long non-coding RNA HOXB-AS1 is a prognostic marker and promotes hepatocellular carcinoma cells’ proliferation and invasion
  63. Preparation and evaluation of LA-PEG-SPION, a targeted MRI contrast agent for liver cancer
  64. Proteomic analysis of the liver regulating lipid metabolism in Chaohu ducks using two-dimensional electrophoresis
  65. Nasopharyngeal tuberculosis: A case report
  66. Characterization and evaluation of anti-Salmonella enteritidis activity of indigenous probiotic lactobacilli in mice
  67. Aberrant pulmonary immune response of obese mice to periodontal infection
  68. Bacteriospermia – A formidable player in male subfertility
  69. In silico and in vivo analysis of TIPE1 expression in diffuse large B cell lymphoma
  70. Effects of KCa channels on biological behavior of trophoblasts
  71. Interleukin-17A influences the vulnerability rather than the size of established atherosclerotic plaques in apolipoprotein E-deficient mice
  72. Multiple organ failure and death caused by Staphylococcus aureus hip infection: A case report
  73. Prognostic signature related to the immune environment of oral squamous cell carcinoma
  74. Primary and metastatic squamous cell carcinoma of the thyroid gland: Two case reports
  75. Neuroprotective effects of crocin and crocin-loaded niosomes against the paraquat-induced oxidative brain damage in rats
  76. Role of MMP-2 and CD147 in kidney fibrosis
  77. Geometric basis of action potential of skeletal muscle cells and neurons
  78. Babesia microti-induced fulminant sepsis in an immunocompromised host: A case report and the case-specific literature review
  79. Role of cerebellar cortex in associative learning and memory in guinea pigs
  80. Application of metagenomic next-generation sequencing technique for diagnosing a specific case of necrotizing meningoencephalitis caused by human herpesvirus 2
  81. Case report: Quadruple primary malignant neoplasms including esophageal, ureteral, and lung in an elderly male
  82. Long non-coding RNA NEAT1 promotes angiogenesis in hepatoma carcinoma via the miR-125a-5p/VEGF pathway
  83. Osteogenic differentiation of periodontal membrane stem cells in inflammatory environments
  84. Knockdown of SHMT2 enhances the sensitivity of gastric cancer cells to radiotherapy through the Wnt/β-catenin pathway
  85. Continuous renal replacement therapy combined with double filtration plasmapheresis in the treatment of severe lupus complicated by serious bacterial infections in children: A case report
  86. Simultaneous triple primary malignancies, including bladder cancer, lymphoma, and lung cancer, in an elderly male: A case report
  87. Preclinical immunogenicity assessment of a cell-based inactivated whole-virion H5N1 influenza vaccine
  88. One case of iodine-125 therapy – A new minimally invasive treatment of intrahepatic cholangiocarcinoma
  89. S1P promotes corneal trigeminal neuron differentiation and corneal nerve repair via upregulating nerve growth factor expression in a mouse model
  90. Early cancer detection by a targeted methylation assay of circulating tumor DNA in plasma
  91. Calcifying nanoparticles initiate the calcification process of mesenchymal stem cells in vitro through the activation of the TGF-β1/Smad signaling pathway and promote the decay of echinococcosis
  92. Evaluation of prognostic markers in patients infected with SARS-CoV-2
  93. N6-Methyladenosine-related alternative splicing events play a role in bladder cancer
  94. Characterization of the structural, oxidative, and immunological features of testis tissue from Zucker diabetic fatty rats
  95. Effects of glucose and osmotic pressure on the proliferation and cell cycle of human chorionic trophoblast cells
  96. Investigation of genotype diversity of 7,804 norovirus sequences in humans and animals of China
  97. Characteristics and karyotype analysis of a patient with turner syndrome complicated with multiple-site tumors: A case report
  98. Aggravated renal fibrosis is positively associated with the activation of HMGB1-TLR2/4 signaling in STZ-induced diabetic mice
  99. Distribution characteristics of SARS-CoV-2 IgM/IgG in false-positive results detected by chemiluminescent immunoassay
  100. SRPX2 attenuated oxygen–glucose deprivation and reperfusion-induced injury in cardiomyocytes via alleviating endoplasmic reticulum stress-induced apoptosis through targeting PI3K/Akt/mTOR axis
  101. Aquaporin-8 overexpression is involved in vascular structure and function changes in placentas of gestational diabetes mellitus patients
  102. Relationship between CRP gene polymorphisms and ischemic stroke risk: A systematic review and meta-analysis
  103. Effects of growth hormone on lipid metabolism and sexual development in pubertal obese male rats
  104. Cloning and identification of the CTLA-4IgV gene and functional application of vaccine in Xinjiang sheep
  105. Antitumor activity of RUNX3: Upregulation of E-cadherin and downregulation of the epithelial–mesenchymal transition in clear-cell renal cell carcinoma
  106. PHF8 promotes osteogenic differentiation of BMSCs in old rat with osteoporosis by regulating Wnt/β-catenin pathway
  107. A review of the current state of the computer-aided diagnosis (CAD) systems for breast cancer diagnosis
  108. Bilateral dacryoadenitis in adult-onset Still’s disease: A case report
  109. A novel association between Bmi-1 protein expression and the SUVmax obtained by 18F-FDG PET/CT in patients with gastric adenocarcinoma
  110. The role of erythrocytes and erythroid progenitor cells in tumors
  111. Relationship between platelet activation markers and spontaneous abortion: A meta-analysis
  112. Abnormal methylation caused by folic acid deficiency in neural tube defects
  113. Silencing TLR4 using an ultrasound-targeted microbubble destruction-based shRNA system reduces ischemia-induced seizures in hyperglycemic rats
  114. Plant Sciences
  115. Seasonal succession of bacterial communities in cultured Caulerpa lentillifera detected by high-throughput sequencing
  116. Cloning and prokaryotic expression of WRKY48 from Caragana intermedia
  117. Novel Brassica hybrids with different resistance to Leptosphaeria maculans reveal unbalanced rDNA signal patterns
  118. Application of exogenous auxin and gibberellin regulates the bolting of lettuce (Lactuca sativa L.)
  119. Phytoremediation of pollutants from wastewater: A concise review
  120. Genome-wide identification and characterization of NBS-encoding genes in the sweet potato wild ancestor Ipomoea trifida (H.B.K.)
  121. Alleviative effects of magnetic Fe3O4 nanoparticles on the physiological toxicity of 3-nitrophenol to rice (Oryza sativa L.) seedlings
  122. Selection and functional identification of Dof genes expressed in response to nitrogen in Populus simonii × Populus nigra
  123. Study on pecan seed germination influenced by seed endocarp
  124. Identification of active compounds in Ophiopogonis Radix from different geographical origins by UPLC-Q/TOF-MS combined with GC-MS approaches
  125. The entire chloroplast genome sequence of Asparagus cochinchinensis and genetic comparison to Asparagus species
  126. Genome-wide identification of MAPK family genes and their response to abiotic stresses in tea plant (Camellia sinensis)
  127. Selection and validation of reference genes for RT-qPCR analysis of different organs at various development stages in Caragana intermedia
  128. Cloning and expression analysis of SERK1 gene in Diospyros lotus
  129. Integrated metabolomic and transcriptomic profiling revealed coping mechanisms of the edible and medicinal homologous plant Plantago asiatica L. cadmium resistance
  130. A missense variant in NCF1 is associated with susceptibility to unexplained recurrent spontaneous abortion
  131. Assessment of drought tolerance indices in faba bean genotypes under different irrigation regimes
  132. The entire chloroplast genome sequence of Asparagus setaceus (Kunth) Jessop: Genome structure, gene composition, and phylogenetic analysis in Asparagaceae
  133. Food Science
  134. Dietary food additive monosodium glutamate with or without high-lipid diet induces spleen anomaly: A mechanistic approach on rat model
  135. Binge eating disorder during COVID-19
  136. Potential of honey against the onset of autoimmune diabetes and its associated nephropathy, pancreatitis, and retinopathy in type 1 diabetic animal model
  137. FTO gene expression in diet-induced obesity is downregulated by Solanum fruit supplementation
  138. Physical activity enhances fecal lactobacilli in rats chronically drinking sweetened cola beverage
  139. Supercritical CO2 extraction, chemical composition, and antioxidant effects of Coreopsis tinctoria Nutt. oleoresin
  140. Functional constituents of plant-based foods boost immunity against acute and chronic disorders
  141. Effect of selenium and methods of protein extraction on the proteomic profile of Saccharomyces yeast
  142. Microbial diversity of milk ghee in southern Gansu and its effect on the formation of ghee flavor compounds
  143. Ecology and Environmental Sciences
  144. Effects of heavy metals on bacterial community surrounding Bijiashan mining area located in northwest China
  145. Microorganism community composition analysis coupling with 15N tracer experiments reveals the nitrification rate and N2O emissions in low pH soils in Southern China
  146. Genetic diversity and population structure of Cinnamomum balansae Lecomte inferred by microsatellites
  147. Preliminary screening of microplastic contamination in different marine fish species of Taif market, Saudi Arabia
  148. Plant volatile organic compounds attractive to Lygus pratensis
  149. Effects of organic materials on soil bacterial community structure in long-term continuous cropping of tomato in greenhouse
  150. Effects of soil treated fungicide fluopimomide on tomato (Solanum lycopersicum L.) disease control and plant growth
  151. Prevalence of Yersinia pestis among rodents captured in a semi-arid tropical ecosystem of south-western Zimbabwe
  152. Effects of irrigation and nitrogen fertilization on mitigating salt-induced Na+ toxicity and sustaining sea rice growth
  153. Bioengineering and Biotechnology
  154. Poly-l-lysine-caused cell adhesion induces pyroptosis in THP-1 monocytes
  155. Development of alkaline phosphatase-scFv and its use for one-step enzyme-linked immunosorbent assay for His-tagged protein detection
  156. Development and validation of a predictive model for immune-related genes in patients with tongue squamous cell carcinoma
  157. Agriculture
  158. Effects of chemical-based fertilizer replacement with biochar-based fertilizer on albic soil nutrient content and maize yield
  159. Genome-wide identification and expression analysis of CPP-like gene family in Triticum aestivum L. under different hormone and stress conditions
  160. Agronomic and economic performance of mung bean (Vigna radiata L.) varieties in response to rates of blended NPS fertilizer in Kindo Koysha district, Southern Ethiopia
  161. Influence of furrow irrigation regime on the yield and water consumption indicators of winter wheat based on a multi-level fuzzy comprehensive evaluation
  162. Discovery of exercise-related genes and pathway analysis based on comparative genomes of Mongolian originated Abaga and Wushen horse
  163. Lessons from integrated seasonal forecast-crop modelling in Africa: A systematic review
  164. Evolution trend of soil fertility in tobacco-planting area of Chenzhou, Hunan Province, China
  165. Animal Sciences
  166. Morphological and molecular characterization of Tatera indica Hardwicke 1807 (Rodentia: Muridae) from Pothwar, Pakistan
  167. Research on meat quality of Qianhua Mutton Merino sheep and Small-tail Han sheep
  168. SI: A Scientific Memoir
  169. Suggestions on leading an academic research laboratory group
  170. My scientific genealogy and the Toronto ACDC Laboratory, 1988–2022
  171. Erratum
  172. Erratum to “Changes of immune cells in patients with hepatocellular carcinoma treated by radiofrequency ablation and hepatectomy, a pilot study”
  173. Erratum to “A two-microRNA signature predicts the progression of male thyroid cancer”
  174. Retraction
  175. Retraction of “Lidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis”
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 8.12.2025 from https://www.degruyterbrill.com/document/doi/10.1515/biol-2022-0471/html
Scroll to top button