Volume 17, Issue 4

SYNOPSIS The function of sleep is one of the most persistent and perplexing mysteries in biology. Many theories have been proposed to explain why we sleep, but most account for only a portion of sleep behavior and very few enjoy strong experimental support. A critical review of current findings leads to the following conclusions. Sleep is for the brain rather than the body, and the neural process most impacted by sleep is cognition. Sleep may influence cognition in many ways, including the removal of a toxic byproduct of wakefulness, or the restoration of neural substrates needed for mental processes. The evidence for these possibilities, however, is weak or equivocal. On the other hand, converging lines of evidence support the hypothesis that sleep promotes brain plasticity.

SYNOPSIS Addiction to opiates such as morphine is a major public health concern. A more thorough understanding of the molecular mechanisms of opiate addiction can lead to better treatment options in the future. Many of the changes in neuronal activity that occur upon morphine exposure have been known for some time, but until recently, little was known about the changes in gene expression that underlie these effects. Recent advances in molecular biology such as microarray analysis and quantitative (real time) PCR have allowed us to examine the gene expression changes that occur in response to morphine treatments and during morphine withdrawal. This review summarizes many of the known molecular and cellular actions of morphine, and some of the important gene expression changes that occur in response to morphine treatment. Many of these gene expression changes underlie the alterations in neuronal excitability, cell morphology and cell birth or death responsible for producing morphine's rewarding effects, the development of dependence, and withdrawal symptoms after treatment ends.

SYNOPSIS Neurons and synapses in the mammalian brain exhibit plastic changes, which occur not only during development and under physiological conditions, but also under pathological conditions. One major cellular hypothesis is that activity-dependent changes in synaptic strength may contribute to the formation of memory and the expression of persistent inflammatory pain. Recently, the anterior cingulate cortex (ACC) has been proposed to play an important role for learning, memory and chronic pain. Long-term potentiation (LTP) and long-term depression (LTD) are well-studied phenomena which may be related to learning and memory. NMDA receptors are the most important trigger for LTP and LTD of synaptic strength. Here, we review recent studies and present new experimental data on the roles of NMDA receptors during synaptic depression in the ACC. Furthermore, we consider the physiological and pathological significance of LTD in the ACC.

SYNOPSIS The posterior parietal cortex plays an important role in visual-spatial attention. Imaging studies reveal consistent parietal activation in attention tasks, while lesions to this area produce significant perceptual deficits. Non-human primate models have been particularly informative in investigating the neurophysiology of attention. The activity of posterior parietal neurons to the same operant stimuli is modulated by whether they are attended or not based on prior information, or whether they attract attention by virtue of their saliency. Posterior parietal neuronal activity appears to provide critical information for shifting attention between stimuli and spatial locations.

SYNOPSIS Alzheimer's disease (AD) is a dementing neurodegenerative disorder for which effective disease-modifying therapeutic treatments have not yet been developed. Genetic and molecular biological studies provide accumulating evidence supporting the hypothesis that the production of amyloid-ß (Aß) peptides, especially neurotoxic Aß42, is central to the pathophysiology of AD - the 'amyloid cascade' hypothesis. Aß is proteolytically generated from a type I integral membrane amyloid precursor protein by the sequential action of two enzymes, called β- and γ-secretase, in reference to their cleavage sites at the N- and C-terminals, respectively. Given the strong association between Aß and AD, the strategies to inhibit the production of Aß, the first step of the amyloid cascade, should prove beneficial as truly disease-modifying therapeutic approaches for the treatment of AD. Recent advances in genetic strategies including knockouts, transgenics and virus-delivered small interfering RNAs and the development of potent and specific small-molecule inhibitors have opened a new window to test the impacts of β- and γ-secretase inhibition in vivo. Since cognitive deficits are at the heart of AD, one of the most important challenges is to determine the therapeutic potential of secretase-inhibiting approaches for AD-related memory deficits, linking perspectives through the prism of molecular/pathological events and those through behavioral and neurophysiological manifestations. I review recent progress in this field, with special focus on the functional consequences of β- and γ-secretase inhibition and altered amyloid neuropathology in mouse models of AD memory deficits.

SYNOPSIS One of the central goals of neuroscience is to elucidate the link between behavior and neuronal activity at both single neuron level and the level of neuronal ensembles. New analytical approaches and techniques constantly emerge that correlate neural activity with perception and behavior with ever finer temporal and spatial scales. In this article I review some of these approaches employed in studies of visual perception in which perceptual reports were required from subjects. I divide these methods into 'correlational' methods and 'perturbation' methods; the former measures normal neural activity and correlates it with behavior, the latter perturbs normal neural activity to cause behavioral alterations. I compare such approaches applied to primates with those applied to human subjects, and discuss how these approaches could be combined and made more powerful in the future.