Neuroscience has long been focused on understanding neural plasticity in both development and adulthood. Experimental work in this area has focused almost entirely on plasticity at excitatory synapses. A growing body of evidence suggests that plasticity at inhibitory GABAergic and glycinergic synapses is of critical importance during both development and aging. The book brings together the work of researchers investigating inhibitory plasticity at many levels of analysis and in several different preparations. This topic is of wide relevance across a number of different areas of research in neuroscience and neurology. Medical problems such as epilepsy, mental illness, drug abuse, and movement disorders can result from malfunctioning inhibitory circuits. Further, the maturation of inhibitory circuits may trigger the onset of critical periods of neural circuit plasticity, raising the possibility that such plastici periods could be reactivated for medical benefit by manipulating inhibitory circuitry.

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.

There seems little doubt that from the earliest evolutionary beginnings, inhibition has been a fundamental feature of neuronal circuits - even the simplest life forms sense and interact with their environment, orienting or approaching positive stimuli while avoiding aversive stimuli. This requires internal signals that both drive and suppress behavior. Traditional descriptions of inhibition sometimes limit its role to the suppression of action potential generation. This view fails to capture the vast breadth of inhibitory function now known to exist in neural circuits. A modern perspective on inhibitory signaling comprises a multitude of mechanisms. For example, inhibition can act via a shunting mechanism to speed the membrane time constant and reduce synaptic integration time. It can act via G-protein coupled receptors to initiate second messenger cascades that influence synaptic strength. Inhibition contributes to rhythm generation and can even activate ion channels that mediate inward currents to drive action potential generation. Inhibition also appears to play a role in shaping the properties of neural circuitry over longer time scales. Experience-dependent synaptic plasticity in developing and mature neural circuits underlies behavioral memory and has been intensively studied over the past decade. At excitatory synapses, adjustments of synaptic efficacy are regulated predominantly by changes in the number and function of postsynaptic glutamate receptors. There is, however, increasing evidence for inhibitory modulation of target neuron excitability playing key roles in experience-dependent plasticity. One reason for our limited knowledge about plasticity at inhibitory synapses is that in most circuits, neurons receive convergent inputs from disparate sources. This problem can be overcome by investigating inhibitory circuits in a system with well-defined inhibitory nuclei and projections, each with a known computational function. Compared to other sensory systems, the auditory system has evolved a large number of subthalamic nuclei each devoted to processing distinct features of sound stimuli. This information once extracted is then re-assembled to form the percept the acoustic world around us. The well-understood function of many of these auditory nuclei has enhanced our understanding of inhibition's role in shaping their responses from easily distinguished inhibitory inputs. In particular, neurons devoted to processing the location of sound sources receive a complement of discrete inputs for which in vivo activity and function are well understood. Investigation of these areas has led to significant advances in understanding the development, physiology, and mechanistic underpinnings of inhibition that apply broadly to neuroscience. In this series of papers, we provide an authoritative resource for those interested in exploring the variety of inhibitory circuits and their function in auditory processing. We present original research and focused reviews touching on development, plasticity, anatomy, and evolution of inhibitory circuitry. We hope our readers will find these papers valuable and inspirational to their own research endeavors.

Traumatic brain injury (TBI) remains a significant source of death and permanent disability, contributing to nearly one-third of all injury related deaths in the United States and exacting a profound personal and economic toll. Despite the increased resources that have recently been brought to bear to improve our understanding of TBI, the developme

The cerebral cortex encodes sensory information with astonishing precision, but it is also confronted with the impressive task of reworking and rewiring its physiology in the face of a changing environment. Hubel and Weisel first characterized the impact of sensory deprivation on the development of cortical response properties, but there is still much we do not know about which forms of cortical plasticity are induced with sensory deprivation, as well as which cell types and synapses mediate plasticity. While traditional models of cortical plasticity proposed Hebbian ("use it or lose it") rules in excitatory circuits as the primary substrate for cortical plasticity, recent advances to the classical model include an important role for non-Hebbian forms of plasticity, and show that inhibitory circuits are a major site of sensory plasticity. A precisely regulated balance between cortical excitation and inhibition is crucial for sensory processing and plasticity, but our understanding of inhibitory synapse development is lacking. Here we investigate the impact of sensory experience on the development and function of inhibitory synapses in rat primary somatosensory cortex. I deprived the D-row of rat whiskers (beginning on the 7th postnatal day, P7) in order to probe how experience guides inhibitory synapse development. I found that deprivation reduced inhibitory currents at P15 in layer (L) 4 and at P21 in L2/3. Evoked inhibition was also reduced at P15 in L4. This reduction in inhibition constitutes a homeostatic form of plasticity, as it would ultimately increase excitatory activity in response to sensory deprivation. Surprisingly, inhibitory currents recovered to control (spared) levels after this one-day period. Our findings demonstrate that the development of inhibitory signaling in S1 during the first postnatal month occurs in a largely experience-independent fashion, but that sensory deprivation during this period causes a delayed and transient reduction in the efficacy of inhibitory signaling. Our results also reveal that these transient changes in mIPSC amplitude and frequency can be dissociated, meaning that they are mechanistically independent. These results add to the growing body of evidence that inhibitory circuits undergo homeostatic plasticity in response to sensory use and disuse in primary sensory cortex.

This volume makes clear that the cognitive and behavioural symptoms of neurologic disorders and syndromes are dynamic and changing. Each chapter describes the neuroplastic processes at work in a particular condition, giving rise to these ongoing cognitive changes.