The Neuroscientist current issue

The Neuroscientist Comments

2009-05-12

Perspectives on Neuroscience and Behavior

2009-05-12

Disease Mechanisms in Neuroscience

2009-05-12

GABA Vesicles at Synapses: Are There 2 Distinct Pools?

Hablitz, J. J., Mathew, S. S., Pozzo-Miller, L. — 2009-05-12

Fast synaptic inhibition in the neocortex is mediated by the neurotransmitter GABA, acting on GABA_A receptors. Neurotransmitters, including GABA, are stored in synaptic vesicles at presynaptic nerve terminals. A long-held assumption has been that evoked and spontaneous neurotransmissions draw on the same pools of vesicles. We review the evidence from FM1-43 studies supporting the contention that at least 2 distinct pools of GABA vesicles are present at inhibitory synapses in the rat neocortex. FM1-43 uptake during spontaneous vesicle endocytosis labels a vesicle pool within neocortical inhibitory nerve terminals that is released much more slowly ("reluctant" pool) than those vesicles loaded by electrical stimulation of afferent fibers or hyperkalemic solutions. These multiple pools may play diverse roles in such processes as long-term depression and/or potentiating of inhibitory synaptic transmission, homeostatic plasticity of inhibitory activity, or developmental changes in inhibitory synaptic transmission.

Degenerate T-Cell Receptor Recognition, Autoreactive Cells, and the Autoimmune Response in Multiple Sclerosis

Markovic-Plese, S. — 2009-05-12

Multiple sclerosis (MS) is the leading cause of disability in the young adult population. While the immunopathogenetic mechanisms that drive the disease have been extensively studied, the autoantigens that trigger the chronic central nervous system inflammation are still not identified. Flexibility/ degeneracy of the T-cell receptor (TCR) in antigen recognition could have a physiological role in thymic selection and the development of comprehensive TCR repertoire and protection from infections. Here, the author explores the possibility that such flexibility/degeneracy may also play a role in the induction of autoimmune diseases. Major histocompatibility complex (MHC) class II alleles of the DR2 haplotype DR2a (DRB5*0101) and DR2b (DRB1*1501) are genes associated with an increased risk for MS in Caucasian populations. Peptide binding to the MHC molecule is a prerequisite for recognition by TCRs, whereby the CD4+ T-cell response is restricted by specific MHC class II DR molecules. To selectively expand and characterize DR2-restricted T-cells with degenerate TCR (TCR_deg), the authors designed MHC class II DR2-anchored peptide mixtures, which preferentially bind to the DR2a and DR2b antigen-presenting molecules. Peptides in these mixtures have specific amino acids in the DR2 binding positions but have randomized amino acids at all other positions of the peptide. Due to the low concentration of individual peptides in these mixtures/libraries, the authors assume that only T-cells with TCR_deg will proliferate in response to these mixtures. The authors have recently identified an increased DR2 restricted TCR_deg T-cell frequency in MS patients in comparison to healthy controls, their cross-reactivity to myelin basic protein, and the secretion of proinflammatory cytokines, all of which suggest that these cells may play a role in the development of the autoimmune response in MS.

The Predictive Brain State: Asynchrony in Disorders of Attention?

Ghajar, J., Ivry, R. B. — 2009-05-12

It is postulated that a key function of attention in goal-oriented behavior is to reduce performance variability by generating anticipatory neural activity that can be synchronized with expected sensory information. A network encompassing the prefrontal cortex, parietal lobe, and cerebellum may be critical in the maintenance and timing of such predictive neural activity. Dysfunction of this temporal process may constitute a fundamental defect in attention, causing working memory problems, distractibility, and decreased awareness.

The Role of the Ubiquitin Proteasome System in Ischemia and Ischemic Tolerance

Meller, R. — 2009-05-12

Ubiquitin modification targets a protein for rapid degradation by the proteasome. However, polyubiquitination of proteins can result in multiple functions depending on the topology of the ubiquitin chain. Therefore, ubiquitin signaling offers a more complex and versatile biology compared with many other posttranslational modifications. One area of potential for the application of this knowledge is the field of ischemia-induced brain damage, as occurs following a stroke. The ubiquitin proteasome system may exert a dual role on neuronal outcome following ischemia. Harmful ischemia results in an overload of the ubiquitin proteasome system, and blocking the proteasome reduces brain infarction following ischemia. However, the rapid and selective degradation of proteins following brief ischemia results in endogenous protection against ischemia. Therefore, further understanding of the molecular signaling mechanisms that regulate the ubiquitin proteasome system may reveal novel therapeutic targets to reduce brain damage when ischemia is predicted or reduce the activation of the cell death mechanisms and the inflammatory response following stroke. The aim of this review is to discuss some of the recent advances in the understanding of protein ubiquitination and its implications for novel stroke therapies.

How Humans Count: Numerosity and the Parietal Cortex

Piazza, M., Izard, V. — 2009-05-12

Numerosity (the number of objects in a set), like color or movement, is a basic property of the environment. Animal and human brains have been endowed by evolution by mechanisms based on parietal circuitry for representing numerosity in an highly abstract, although approximate fashion. These mechanisms are functional at a very early age in humans and spontaneously deployed in the wild by animals of different species. The recent years have witnessed terrific advances in unveiling the neural code(s) underlying numerosity representations and showing similarities as well as differences across species. In humans, during development, with the introduction of symbols for numbers and the implementation of the counting routines, the parietal system undergoes profound (yet still largely mysterious) modifications, such that the neural machinery previously evolved to represent approximate numerosity gets partially "recycled" to support the representation of exact number.

Color Vision, Cones, and Color-Coding in the Cortex

Conway, B. R. — 2009-05-12

Color processing begins with the absorption of light by cone photoreceptors, and progresses through a series of hierarchical stages: Retinal signals carrying color information are transmitted through the lateral geniculate nucleus of the thalamus (LGN) up to the primary visual cortex (V1). From V1, the signals are processed by the second visual area (V2); then by cells located in subcompartments ("globs") within the posterior inferior temporal (PIT) cortex, a brain region that encompasses area V4 and brain regions immediately anterior to V4. Color signals are then processed by regions deep within the inferior temporal (IT) cortex including area TE. As a heuristic, one can consider each of these stages to be involved in constructing a distinct aspect of the color percept. The three cone types are the basis for trichromacy; retinal ganglion cells that respond in an opponent fashion to activation of different cone classes are the basis for color opponency (these "cone-opponent" cells increase their firing rate above baseline to activation of one cone class and decrease their firing rate below baseline to activation of a different cone class); double-opponent neurons in the V1 generate local color contrast and are the building blocks for color constancy; glob cells elaborate the perception of hue; and IT integrates color perception in the context of behavior. Finally, though nothing is known, these signals presumably interface with motor programs and emotional centers of the brain to mediate the widely acknowledged emotional salience of color.

Cortical Changes Following Spinal Cord Injury with Emphasis on the Nogo Signaling System

Endo, T., Tominaga, T., Olson, L. — 2009-05-12

After spinal cord injury, structural as well as functional modifications occur in the adult CNS. Sites of plastic changes include the injured spinal cord itself as well as cortical and subcortical structures. Previously, cortical reorganization in response to sensory deprivation has mainly been studied using peripheral nerve injury models, and has led to a degree of understanding of mechanisms underlying reorganization and plastic changes. Deprivation or damage-induced CNS plasticity is not always beneficial for patients, and may underlie the development of conditions such as neuropathic pain and phantom sensations. Therefore, efforts not only to enhance, but also to control the capacity of plastic changes in the CNS, are of clinical relevance. Novel methods to stimulate plasticity as well as to monitor it, such as transcranial magnetic stimulation and functional magnetic resonance imaging, respectively, may be useful in diverse clinical situations such as spinal cord injury and stroke. Here, human and animal studies of spinal cord injury are reviewed, with special emphasis on the contribution of the Nogo signaling system to cortical plasticity.