Inhibitory neurons play a critical role in normal information processing in the neocortex. Moreover, their dysfunction may contribute to the pathophysiology underlying certain disorders. To date, most of our understanding of the diverse functions of inhibitory neurons and their synapses has been revealed through studies of sensory cortices. My long range goal is to determine if dramatic regional differences in local inhibitory networks result in distinct inhibitory and network mechanisms in the neocortex. My work will specifically focus on the medial prefrontal cortex (mPFC) and ventral postrhinal cortex (vPOR), brain areas with remarkably few parvalbumin- (PV) expressing interneurons compared to sensory cortices. The PFC and POR are essential in cognitive control and visuospatial attention, respectively, and their lack of PV- interneurons could play a pivotal role in how these areas normally process information. There are three specific aims in this proposal: 1) To characterize and compare the local inhibitory networks within the mPFC and vPOR;2) To dissect the cellular mechanisms underlying thalamocortical feedforward inhibition in the mPFC and vPOR;3) To determine the cellular mechanisms underlying gamma oscillations in the mPFC and vPOR. All my data will be compared to data I obtain from the primary somatosensory cortex (SI), a leading model for studying the structure and physiology of neocortical circuits. To address these aims I will use a combination of in vitro patch clamp techniques, various optogenetic approaches, quantitative histological methods, and multiple transgenic lines of mice to identify, select, and manipulate activity of specific neurons. My research will illuminate the basic physiology and diversity of neural circuits in the neocortex. It also may shed light on certain neuropsychiatric conditions in which inhibition is compromised.

Public Health Relevance

My research focuses on understanding the basic physiology of neural circuits in the neocortex, a brain region responsible for many higher order brain functions such as perception, language, reasoning, and some forms of memory. A common feature of many neurological disorders, such as epilepsy, autism, and schizophrenia, is altered communication between neurons in the neocortex. Ultimately, my research will help provide a foundation for explaining how the brain performs higher order functions as well as how certain pathophysiological and genetic changes can lead to altered neocortical function.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1)
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Gnadt, James W
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Brown University
Schools of Medicine
United States
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Crandall, Shane R; Cruikshank, Scott J; Connors, Barry W (2015) A corticothalamic switch: controlling the thalamus with dynamic synapses. Neuron 86:768-82
Aerts, Jordan T; Louis, Kathleen R; Crandall, Shane R et al. (2014) Patch clamp electrophysiology and capillary electrophoresis-mass spectrometry metabolomics for single cell characterization. Anal Chem 86:3203-8
Crandall, Shane R; Cox, Charles L (2013) Thalamic microcircuits: presynaptic dendrites form two feedforward inhibitory pathways in thalamus. J Neurophysiol 110:470-80