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 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.

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.

"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"--

Reviews the state of knowledge on the mechanisms of development of mammalian sensory systems and presents new findings on genetically controlled and environmentally contingent patterns of sensory system development. Also reveals major principles deduced from studies of the developing visual, auditory, somatosensory, and chemical sensory systems that are generalizable to other regions of the developing nervous system, and provides insights on the comparative development of sensory system structure and function among mammals, including humans.

Presents an account of the remarkable progress made in different areas of neurobiology. This book introduces the structure and development of the brain, showing how they are specialized for the functions they serve. It is concerned with hormones and neurotransmitters.

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.