Inhibitory Synaptic Plasticity

This volume will explore the most recent findings on cellular mechanisms of inhibitory plasticity and its functional role in shaping neuronal circuits, their rewiring in response to experience, drug addiction and in neuropathology. Inhibitory Synaptic Plasticity will be of particular interest to neuroscientists and neurophysiologists.

Learning and memory are believed to depend on plastic changes of neuronal circuits due to activity-dependent potentiation or depression of specific synapses. During the last two decades, plasticity of brain circuits was hypothesized to mainly rely on the flexibility of glutamatergic excitatory synapses, whereas inhibitory synapses were assumed relatively invariant, to ensure stable and reliable control of the neuronal network. As a consequence, while considerable efforts were made to clarify the main mechanisms underlying plasticity at excitatory synapses, the study of the cellular/molecular mechanisms of inhibitory plasticity has received much less attention. Nevertheless, an increasing body of evidence has revealed that inhibitory synapses undergo several types of plasticity at both pre- and postsynaptic levels. Given the crucial role of inhibitory interneurons in shaping network activities, such as generation of oscillations, selection of cell assemblies and signal integration, modifications of the inhibitory synaptic strength represents an extraordinary source of versatility for the fine control of brain states. This versatility also results from the rich diversity of GABAergic neurons in several brain areas, the specific role played by each inhibitory neuron subtype within a given circuit, and the heterogeneity of the properties and modulation of GABAergic synapses formed by specific interneuron classes. The molecular mechanisms underlying the potentiation or depression of inhibitory synapses are now beginning to be unraveled. At the presynaptic level, retrograde synaptic signaling was demonstrated to modulate GABA release, whereas postsynaptic forms of plasticity involve changes in the number/gating properties of GABAA receptors and/or shifts of chloride gradients. In addition, recent research indicates that GABAergic tonic inhibition can also be plastic, adding a further level of complexity to the control of the excitatory/inhibitory balance in the brain. The present Topic will focus on plasticity of GABAergic synapses, with special emphasis on the molecular mechanisms of plasticity induction and/or expression.

A comprehensive, multidisciplinary review, Neural Plasticity and Memory: From Genes to Brain Imaging provides an in-depth, up-to-date analysis of the study of the neurobiology of memory. Leading specialists share their scientific experience in the field, covering a wide range of topics where molecular, genetic, behavioral, and brain imaging techniq

GABA is the principal inhibitory neurotransmitter in the CNS and acts via GABAA and GABAB receptors. Recently, a novel form of GABAA receptor-mediated inhibition, termed “tonic” inhibition, has been described. Whereas synaptic GABAA receptors underlie classical “phasic” GABAA receptor-mediated inhibition (inhibitory postsynaptic currents), tonic GABAA receptor-mediated inhibition results from the activation of extrasynaptic receptors by low concentrations of ambient GABA. Extrasynaptic GABAA receptors are composed of receptor subunits that convey biophysical properties ideally suited to the generation of persistent inhibition and are pharmacologically and functionally distinct from their synaptic counterparts. This book highlights ongoing work examining the properties of recombinant and native extrasynaptic GABAA receptors and their preferential targeting by endogenous and clinically relevant agents. In addition, it emphasizes the important role of extrasynaptic GABAA receptors in GABAergic inhibition throughout the CNS and identifies them as a major player in both physiological and pathophysiological processes.

Primary sensory neurons respond to peripheral stimulation and project to the spinal cord. Specifically, the population of neurons which respond to damaging stimuli terminate in the superficial layers of the dorsal horn. Therefore, the dorsal horns constitute the first relay site for nociceptive fibre terminals which make synaptic contacts with second order neurons. It has recently become clear that the strength of this first pain synapse is plastic and modifiable by several modulators, including neuronal and non-neuronal regulators, and studies on the fundamental processes regulating the plasticity of the first pain synapse have resulted in the identification of new targets for the treatment of chronic pain. This book will be of interest to a wide readership in the pain field.

This book has brought together leading investigators who work in the new arena of brain connectomics. This includes ‘macro-connectome’ efforts to comprehensively chart long-distance pathways and functional networks; ‘micro-connectome’ efforts to identify every neuron, axon, dendrite, synapse, and glial process within restricted brain regions; and ‘meso-connectome’ efforts to systematically map both local and long-distance connections using anatomical tracers. This book highlights cutting-edge methods that can accelerate progress in elucidating static ‘hard-wired’ circuits of the brain as well as dynamic interactions that are vital for brain function. The power of connectomic approaches in characterizing abnormal circuits in the many brain disorders that afflict humankind is considered. Experts in computational neuroscience and network theory provide perspectives needed for synthesizing across different scales in space and time. Altogether, this book provides an integrated view of the challenges and opportunities in deciphering brain circuits in health and disease.

Jasper's Basic Mechanisms, Fourth Edition, is the newest most ambitious and now clinically relevant publishing project to build on the four-decade legacy of the Jasper's series. In keeping with the original goal of searching for "a better understanding of the epilepsies and rational methods of prevention and treatment.", the book represents an encyclopedic compendium neurobiological mechanisms of seizures, epileptogenesis, epilepsy genetics and comordid conditions. Of practical importance to the clinician, and new to this edition are disease mechanisms of genetic epilepsies and therapeutic approaches, ranging from novel antiepileptic drug targets to cell and gene therapies.