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The major issue in neuroscience is to delineate the structure and function of the neural circuits that mediate a variety of brain functions. One useful approach to resolve this issue is the genetic manipulation of the activity of specific neural circuits, which enables the study of the behavioral and physiological consequences of the manipulation. A novel type of lentiviral vector showing highly efficient retrograde gene transfer (HiRet) can introduce a transgene into neurons that innervate a certain brain region at the vector injection site and confer a fundamental tool for genetically manipulating specific neural pathways. Here, we describe the strategy for the selective targeting of neural pathways by using this HiRet vector, combined with immunotoxin (IT)-mediated cell targeting, which eliminates particular neuronal types genetically engineered to express a receptor for the recombinant IT. Our strategy provides a powerful technology to investigate the framework underlying brain functions and to develop animal models for the dissection of neurological and neuropsychiatric diseases.

New information about the basal ganglia and cerebellar connections with the cerebral cortex has prompted a reevaluation of the role of the basal ganglia in cognition. We know that the relation between the basal ganglia and the cerebral cortical region allows for connections organized into discrete circuits. Rather than serving as a means for widespread cortical areas to gain access to the motor system, these loops reciprocally interconnect a large and diverse set of cerebral cortical areas with the basal ganglia. The properties of neurons within the basal ganglia or cerebellar components of these circuits resemble the properties of neurons within the cortical areas subserved by these loops. For example, neuronal activity within the basal ganglia and cerebellar loops with motor areas of the cerebral cortex is highly correlated with parameters of movement, whereas neuronal activity within the basal ganglia and cerebellar loops with areas of the prefrontal cortex is more related to the aspects of cognitive function. Thus, individual loops appear to be involved in distinct behavioral functions. Studies of the basal ganglia and cerebellar pathology support this conclusion. Damage to the basal ganglia or cerebellar components of circuits with motor areas of the cortex leads to motor symptoms, whereas damage to the subcortical components of circuits with nonmotor areas of the cortex causes higher-order deficits. In this report, we review some of the new anatomic, physiologic, and behavioral findings that have contributed to a reappraisal of function concerning the basal ganglia and cerebellar loops with the cerebral cortex and apply it in clinical applications to obsessive-compulsive disorder, Tourette’s syndrome, and attention-deficit/hyperactivity disorder as examples of how compromise at different points in the system may yield similar but different clinical results.

Animals including humans experience objects in a certain environment, that is, a context. Same objects may have to be treated differently, or different objects may need to be treated similarly depending on contexts. Flexible behavioral choice in such ambiguous situations involves dynamic interactions among brain regions, but underlying neural mechanisms are poorly understood. In this article, prior studies that have examined (mostly in rodents) some of the brain regions involved in contextual processing of object information using goal-directed tasks are selectively reviewed. The current review identifies the hippocampus, prefrontal cortex (PFC) and perirhinal cortex (PER) as key regions for associating the same objects with different reward values and responses depending on the background visual context. The hippocampus is particularly important for contextual choice behavior when the context must be used as a conditional cue that can disambiguate reward-related ‘meanings’ of objects. The PER appears to play significant roles in such tasks during initial learning (but not so much for retrieval) because perturbations in the PER produce severe deficits in the acquisition of the contextual object memory task. Perturbations in the PFC also affect performance when flexible contextual responses should be made toward otherwise ambiguous objects.

Social bonds are important for human health and well-being, and a crucial component of these bonds is the ability to maintain a bond once it has been formed. Importantly, although bond maintenance is required for social attachments, very little is known about the neural mechanisms that mediate this behavior. Recently, laboratory studies utilizing the socially monogamous prairie vole (an excellent animal model for the neurobiology of selective social attachment), have allowed the neural correlates of selective social attachment to begin to unfold. These studies have identified that the activation of both motivational and hedonic processing systems, which mediate other natural rewards, is also important for mediating social behaviors that are characteristic of an established pair bond. These social behaviors include appetitive and positive social interactions with a potential mating partner in sexually naïve prairie voles, the avoidance of novel conspecifics (and sometimes aggressive rejection) that characterizes the established pair bond and, finally, an aversion towards partner separation. The following review will discuss how a balance between opposing endogenous opioid systems – positive (mu-opiod receptors) and aversive (kappa-opioid receptors) – provide essential hedonic signaling that guides socially motivated behaviors.

Melanoma-associated antigen-D1 (MAGE-D1) was discovered in bone marrow stromal cells. MAGE-D1 is detected in progenitor cells in the neuroepithelia and subventricular regions as well as in the postmitotic neuronal cells in the entire brain in the developing embryo and is also detected in most adult tissues, predominantly in the brain. Herein, we provide an overview of the roles of MAGE-D1 in the central nervous system. MAGE-D1 participates in neurotrophin-induced neuronal differentiation and survival by modulating Trk-dependent phosphorylation. MAGE-D1 regulates Dlx-dependent migration-related transcription by binding to necdin or praja-1. MAGE-D1 regulates a number of apoptotic pathways, each caused by distinct input signals, such as bone morphogenetic protein, p75 neurotrophin receptor, and uncoordinated gene-5 homologue. MAGE-D1 knockout mice show depressive behavior and impairments of circadian rhythm caused by decreased ubiquitylation of serotonin transporter and regulated transcription of RORα, respectively. The gene for necdin, a MAGE-D1-binding protein, has been described as responsible for Prader-Willi syndrome. In conclusion, MAGE-D1 plays important roles in the central nervous system in both developmental and adult stages and would be an invaluable target in the development of novel diagnostic and therapeutic agents for depression and Prader-Willi syndrome and also for providing new insights into the pathogenesis/pathophysiology of these diseases.

The previous understanding of multiple sclerosis was solely related to neuroinflammation and its harmful effects; however, countless data indicate the importance of some inflammation-independent, neurodegenerative mechanisms associated with mitochondria malfunction, iron deposition and oxidative stress. Recently, it has been postulated that glutamate excitotoxicity, a phenomenon that takes place when an excessive amount of glutamate overactivates its cellular receptors and induces cell death, could be a missing link between inflammatory and neurodegenerative processes evident in multiple sclerosis. Glutamate is the major excitatory neurotransmitter of the central nervous system, which has been proven to have a central role in a complex communication network established between all residential brain cells, including neurons, astrocytes, oligodendrocytes and microglia. Thus, the disturbance of glutamate homeostasis could affect practically all physiological functions and interactions of brain cells, leading to heterogeneity of pathological events. The understanding of glutamate excitotoxicity as a valid mechanism of central nervous system damage in multiple sclerosis, requires the revision of the current knowledge about a source of elevated extracellular glutamate, glutamate receptor alterations, alterations of glutamate transporters and metabolizing enzymes, as well as molecular mechanism of excitotoxic damage.

It has been suggested that, during evolution, specific mechanisms developed in order to optimize the detection of threats and opportunities even in perceptually degraded conditions. A naturalistic example of perceptual degradation can be found in blurry images, which contain the coarsest elements of a scene (low spatial frequencies) but lack the fine-grained details (high spatial frequencies). In the past decade, several studies have examined the relation between spatial frequencies and emotions, using a variety of methods, stimuli, and rationales. Here, we conduct a literature survey on the studies that have examined the relation between emotion and spatial frequencies. Some studies have suggested that the low spatial frequencies of emotional stimuli may be processed by a subcortical neural pathway, eventually eliciting emotional responses. However, the evidence provided by the reviewed studies does not support this possibility, for conceptual and methodological reasons (e.g., mistaking the processing of a fuzzy stimulus for subcortical processing). Here, the conceptual and methodological problems present in the reviewed studies are analyzed and discussed, along with suggestions for future research.

Background: This evidence-based review reports an updated evaluation and critical appraisal of available studies that investigated the effectiveness of repetitive transcranial magnetic stimulation (rTMS) on post-stroke aphasia rehabilitation. Methods: A literature search was performed to identify studies that investigated the therapeutic effects of rTMS on post-stroke aphasia in various electronic databases, from their inception to 2011. The selected studies were classified according to the types of participants, types of interventions, outcome measures, and results. The methodological qualities of the selected studies were evaluated using the Physiotherapy Evidence Database scale. Results: The current review was based on 12 studies, including open-label designs and controlled trials, that showed a positive effect of rTMS, with or without conventional rehabilitation, on post-stroke aphasia compared with sham or conventional rehabilitation alone. About 41% of the selected studies reported the long-term effect of rTMS on aphasia recovery. No adverse effect was reported. Conclusions: The current review reveals that rTMS with or without conventional rehabilitation has positive effects on post-stroke aphasia. The studies also contributed to the plausible mechanisms of stroke recovery. However, with the concerns over the methodology of the selected studies in this review, a larger-scale, multicenter, well-designed randomized controlled trial involving different phases and types of aphasia needs to be carried out before recommending rTMS as a complementary treatment for post-stroke aphasia.