2013 — 2015 |
Crandall, Shane R |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
Functions of Naturally Diverse Inhibitory Networks in Neocortex
DESCRIPTION (provided by applicant): 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.
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2016 — 2020 |
Crandall, Shane R |
K99Activity Code Description: To support the initial phase of a Career/Research Transition award program that provides 1-2 years of mentored support for highly motivated, advanced postdoctoral research scientists. R00Activity Code Description: To support the second phase of a Career/Research Transition award program that provides 1 -3 years of independent research support (R00) contingent on securing an independent research position. Award recipients will be expected to compete successfully for independent R01 support from the NIH during the R00 research transition award period. |
Dynamic Properties of Corticothalamic Circuits
? DESCRIPTION (provided by applicant): Virtually all sensory information enters the neocortex by way of the thalamus. The neocortex in turn sends a massive projection back to the thalamus. Despite being reciprocally connected partners, we are only beginning to understand the nature of cortex's influence over the thalamus. It is clear that the coordinated activities of these two areas are essential for normal sensation, movement, and cognition. Moreover, altered communication between the thalamus and the neocortex has been associated with certain neurological and psychiatric disorders (e.g., absence epilepsy and schizophrenia). The central goal of my proposal is to understand the dynamic nature and mechanisms underlying corticothalamic circuits while augmenting my research training as I proceed to an independent position. There are three scientific aims in this research proposal: 1) To test the activity-dependent influence of corticothalamic output on the excitability and sensory- evoked responses of aligned thalamic neurons in the anaesthetized animal; 2) To investigate how wakefulness affects the activity-dependent influence of corticothalamic output; 3) To characterize the impact of long-range afferent systems on layer 6 circuit activity and corticothalamic output in both isolated and intact brain preparations. Under the mentorship of Drs. Barry Connors and Christopher Moore and with the support of Drs. Julie Kauer and Scott Cruikshank, I will learn new experimental techniques and develop important career skills essential for success in academia. During the K99 phase of the award, I will develop expertise in in vivo extra- and intra-cellular electrophysiological techniques, optogenetic approaches in vivo, and strategies for monitoring behavior in awake, head-restrained animals. My long-term goal is to take an interdisciplinary approach that includes newly acquired in vivo techniques as well as previously learned skills such as in vitro electrophysiology, optogenetics, two-photon microscopy, calcium imaging, glutamate uncaging, and anatomy to test my own hypotheses about corticothalamic circuitry in both isolated and intact brain preparations (R00 and beyond). My studies should help unravel some of the complexity of the corticothalamic system, and provide a mechanistic understanding of how the neocortex can control its own sensory input.
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