Our long-term objective is to understand the role of cortical GABAA receptor-mediated inhibition in the perception of sensory stimuli, and how modulation of GABAA receptors by general anesthetics and changes in cortical inhibition in various neuropathologies alters sensory perception. In this proposal, we seek to understand how GABAergic cells control the timing of action potentials in auditory cortex (ACx). Firing patterns distributed across populations of pyramidal cells in ACx are postulated to represent certain features of acoustic stimuli. Spikes in these population codes are either time-locked to transitions in the stimulus, or comprise temporal patterns generated internally. Evidence suggests that networks of cortical interneurons are involved in establishing both types of patterns. Thalamocortical (TC) afferents activate multiple populations of 'feedforward' GABAergic interneurons in ACx. Lemniscal TC fibers target cells in layers III and IV (LIII/IV), while extralemniscal TC afferents target cells in layer I (LI). Activation of the latter afferents triggers gamma frequency oscillations in ACx. We propose that feedforward intemeurons in ACx regulate spike timing in pyramidal cells and that this capability is enhanced by network interactions among inhibitory cells. We will test the hypothesis that LI interneurons control internally generated firing patterns, while LIII/IV interneurons coordinate firing patterns that are time-locked to the stimulus. Disruption of cortical timing signals has also been postulated to underlie sensory and cognitive impairment during general anesthesia, and modulation of cortical rhythms in ACx is being pursued as a solution to the important medical application of monitoring depth of anesthesia in patients. GABAergic interneurons are central players in normal, pathological and exogenously modulated cortical processing. Thus, understanding how these cells are activated and organized and the functional implications of this structure is critical to understanding cortical information processing. Although evidence abounds that these cells play a pivotal role in setting the response properties of )rincipal cells, we seek to fill the gap in our knowledge of their organization and how they interact with )rincipal cells.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC006013-06
Application #
7342867
Study Section
Special Emphasis Panel (ZRG1-IFCN-6 (01))
Program Officer
Platt, Christopher
Project Start
2003-03-15
Project End
2009-07-31
Budget Start
2008-02-01
Budget End
2009-01-31
Support Year
6
Fiscal Year
2008
Total Cost
$225,951
Indirect Cost
Name
University of Wisconsin Madison
Department
Physiology
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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Raz, Aeyal; Grady, Sean M; Krause, Bryan M et al. (2014) Preferential effect of isoflurane on top-down vs. bottom-up pathways in sensory cortex. Front Syst Neurosci 8:191
Krause, Bryan M; Banks, Matthew I (2013) Analysis of stimulus-related activity in rat auditory cortex using complex spectral coefficients. J Neurophysiol 110:621-39
Smith, Philip H; Uhlrich, Daniel J; Manning, Karen A et al. (2012) Thalamocortical projections to rat auditory cortex from the ventral and dorsal divisions of the medial geniculate nucleus. J Comp Neurol 520:34-51
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