Neuromodulatory regulation of local circuit computations in the neocortex.

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Bibliographic Details
Author / Creator:Runfeldt, Melissa Jane.
Description:119 p.
Format: E-Resource Dissertations
Local Note:School code: 0330.
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Other authors / contributors:University of Chicago.
Notes:Advisor: Jason N. MacLean.
Thesis (Ph.D.)--The University of Chicago, Division of the Biological Sciences, and The Pritzker School of Medicine, Committee on Computational Neuroscience, 2015.
Dissertation Abstracts International, Volume: 76-08(E), Section: B.
Summary:The neocortical neurochemical environment regulates how information is transmitted and translated through circuits of recurrently connected neurons. In this way, the synaptic structure serves as a dynamic substrate for information processing, where both neuromodulatory environment and glutamatergic drive shape cortical activity. Different stages of sleep and wakefulness are regulated by the release of distinct neuromodulators from subcortical nuclei, which alter signatures of cortical activity and the corresponding computational processes that form ongoing and future perception. Examining how different states alter functional circuitry offers a platform for understanding the relationships between cortical architecture, computational structure, and the processing of sensory information. The work presented here focuses on how norepinepherine (NE) and acetylcholine (ACh), which are the dominant neuromodulatory regulators of wakefulness and attention, alter local cortical circuit activity. By using 2-photon imaging in a thalamo-cortical slice preparation, we can simultaneously record action potential activity from up to 1200 neurons while experimentally controlling thalamic input to the cortex. This experimental model permits the study of cortical processing of afferent information with unprecedented spatial and temporal resolution. Combining 2-photon imaging with whole-cell electrophysiology, and graph with information theory, I show that both ACh and NE induce systematic changes in the functional organization of local cortical circuits. The holistic effect of these modifications is to increase the cortical capacity to resolve (ACh) and transmit (NE) afferent information from the thalamus. These results further our understanding of how the functional structure of cortical circuits can be neurochemically modulated to serve different computational functions.