"Neuroplasticity refers to the brain’s ability to modify its connections and function in response to experience. This experience-dependent plasticity is necessary for the acquisition of new abilities during early development or in adult life, and plays a crucial role in recovery after a neurological injury. During early developmental epochs known as critical periods (CPs), passive experience alone can have profound and long-lasting effects in cortical sensory representations. In contrast, plasticity in the adult brain occurs almost exclusively in the context of perceptual learning (PL); i.e., the process whereby attention and repetition lead to long-lasting improvements in stimulus detection or sensory discrimination.Whether it occurs as a result of passive experience, PL, or other experimental interventions, cortical plasticity ultimately entails a change in activity patterns driven by a shift in the local levels of excitation and inhibition. And although cortical inhibitory interneurons constitute a clear minority compared to the number of excitatory neurons, they are instrumental in regulating both juvenile and adult experience-dependent plasticity. This thesis consists of three experimental studies that addressed critical and interrelated knowledge gaps regarding the inhibitory regulating mechanisms of experience-dependent plasticity, both in the context of changes in the environment and during PL. Using the rat primary auditory cortex (A1) as a model, we combined electrophysiological, anatomical, chemogenetic, and behavioral methodologies to address each study’s main hypotheses. In the first study we examined the role of inhibition in A1 plasticity across the lifespan. We found that reduced cortical inhibition in older adults was associated with an increased but poorly regulated plasticity when compared to younger adults. In older brains, however, changes elicited by auditory stimulation and training were rapidly lost, suggesting that such increased plasticity might be detrimental, as the older brains were unable to consolidate these changes. Importantly, increasing inhibition artificially with clinically available drugs restored the stability of sensory representations and improved the retention of plastic changes associated with PL.In the second study, we turned our attention to parvalbumin-positive (PV+) cells, the most common type of inhibitory neurons in the brain. Bidirectional manipulation of PV+ cell activity affected neuronal spectral and sound intensity selectivity, and, in the case of PV+ interneuron inactivation, was mirrored by anatomical changes in PV and associated perineuronal net expression. In addition, we showed that the inactivation of PV+ interneurons is sufficient to reinstate CP plasticity in the adult auditory cortex. In the third study, we investigated the role of PV+ cells in auditory PL. As previously reported in other cortical areas, training was associated with a transient downregulation of PV expression during early stages of training. We then examined the effects of prolonged PV+ cell manipulation throughout the training period. Our results suggest that, although reduced PV+ cell function may facilitate early training-related modifications in cortical circuits, a subsequent increase in PV+ cell activity is needed to prevent further plastic changes and consolidate learning. Taken together, our findings underscore the importance of sustained inhibitory neurotransmission in ensuring high fidelity discrimination of sensory inputs and in maintaining the stability of sensory representations. Our behavioral studies further suggest that such stability is necessary for the consolidation of complex skills that are built on basic sensory representations. Finally, the experimental work presented in this thesis also highlights the potential of pharmacological and chemogenetic approaches for harnessing cortical plasticity with the ultimate goal of aiding recovery from brain injury or disease"--

Plasticity of synapses is not static across the lifespan. As the brain matures and ages, the ability of neurons to undergo structural and functional change becomes more limited. Further, there are a number of modulatory factors that influence the expression of synaptic plasticity. Here, three approaches were taken to examine and manipulate plasticity in the auditory thalamocortical system of rats. Using an in vivo preparation, long-term potentiation (LTP) and paired pulse (PP) responses were used as measures of long- and short-term plasticity, respectively. First, the effect of intracortical zinc application in the primary auditory cortex (A1) on LTP was examined. Following theta burst stimulation (TBS) of the medial geniculate nucleus (MGN), juvenile and middle-age rats, but not young adults, showed greater levels of LTP with zinc application relative to age-matched control animals. Next, PP responses were examined between rats reared in unaltered acoustic conditions and those reared in continuous white noise (WN) from postnatal day (PD) 5 to PD 50-60 (i.e., subjected to patterned sound deprivation). Rats reared in WN demonstrated less PP depression relative to controls, indicating that WN rearing alters short-term thalamocortical synaptic responses. Furthermore, control males showed no change in PP response following LTP induction, indicating a postsynaptic locus of LTP, whereas increased PP depression following LTP induction was seen in WN animals, suggestive of a presynaptic involvement in LTP. Finally, differences in plasticity between male and female rats were investigated, and the result of early WN exposure on both sexes was examined. Males and females did not show consistent differences in LTP expression; however WN exposure appeared to affect LTP of females less than their male counterparts. PP responses were then compared between WN-reared males and females, and no difference was found. This indicates that short-term plastic properties of auditory thalamocortical synapses between the sexes do not differ, even though plasticity on a longer time scale following sensory deprivation does indicate some difference. Together, the experiments summarized here identify some of the important factors that contribute to the regulation of short- and long-term synaptic plasticity in the central auditory system of the mammalian brain.

Recent studies show that more people than ever before are reaching old age in better health and enjoying that health for a longer time. This Handbook outlines the latest discoveries in the study of aging from bio-medicine, psychology, and socio-demography. It treats the study of aging as a multidisciplinary scientific subject, since it requires the interplay of broad disciplines, while offering high motivation, positive attitudes, and behaviors for aging well, and lifestyle changes that will help people to stay healthier across life span and in old age. Written by leading scholars from various academic disciplines, the chapters delve into the most topical aspects of aging today - including biological mechanisms of aging, aging with health, active and productive aging, aging with satisfaction, aging with respect, and aging with dignity. Aimed at health professionals as well as general readers, this Cambridge Handbook offers a new, positive approach to later life.

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

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.

This volume brings together authors working on a wide range of topics to provide an up to date account of the underlying mechanisms and functions of neurogenesis and synaptogenesis in the adult brain. With an increasing understanding of the role of neurogenesis and synaptogenesis it is possible to envisage improvements or novel treatments for a number of diseases and the possibility of harnessing these phenomena to reduce the impact of ageing and to provide mechanisms to repair the brain.

There has been substantial progress in understanding the contributions of the auditory forebrain to hearing, sound localization, communication, emotive behavior, and cognition. The Auditory Cortex covers the latest knowledge about the auditory forebrain, including the auditory cortex as well as the medial geniculate body in the thalamus. This book will cover all important aspects of the auditory forebrain organization and function, integrating the auditory thalamus and cortex into a smooth, coherent whole. Volume One covers basic auditory neuroscience. It complements The Auditory Cortex, Volume 2: Integrative Neuroscience, which takes a more applied/clinical perspective.