The broad goal of the proposal is to understand the functional organization of the early thalamocortical stages of processing in the auditory system. This involves a better functional understanding of the various pathways connecting the medial geniculate body (MGB) plus first and second auditory cortices (A1 and A2). We will use an in vitro slice preparation of the mouse brain in which different slice configurations will have the MGB to A1/A2, A1 to MGB, and A1 to A2 pathways intact. We will use uncaging of glutamate by photostimulation or minimal electrical stimulation to test the function of each of these glutamatergic pathways, and this will be complemented by the use of channelrhodopsin methodology. In particular, we shall attempt to classify each pathway as Class 1 (i.e., formerly """"""""driver""""""""), Class 2 (formerly """"""""modulator""""""""), or other, and thereby we hope to construct a functional hierarchy of information flow. We shall also test the role of layer 6 corticothalamic cells in gating thalamocortical transmission and test the complex hypothesis, first, that there exists parallel direct and corticothalamocortical pathways linking A1 with A2, and second, that these dual pathways operate in a coincidence detection manner to control information flow. This could also provide more general insights regarding cortical functioning, particularly with respect to new evidence that different cortical areas can dynamically cooperate depending on behavioral needs.

Public Health Relevance

We must better understand auditory information flow through the first few stages of cortical processing to begin to understand how pathology in these pathways leads to hearing loss including defects in cognitive auditory functions, such as lexical-semantic processing, phonological information extraction, selective attention and object recognition.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC008794-07
Application #
8408787
Study Section
Cognitive Neuroscience Study Section (COG)
Program Officer
Platt, Christopher
Project Start
2007-02-08
Project End
2017-01-31
Budget Start
2013-02-01
Budget End
2014-01-31
Support Year
7
Fiscal Year
2013
Total Cost
$314,925
Indirect Cost
$113,050
Name
University of Chicago
Department
Biology
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Sherman, S Murray (2016) Thalamus plays a central role in ongoing cortical functioning. Nat Neurosci 19:533-41
Liu, Tingting; Petrof, Iraklis; Sherman, S Murray (2015) Modulatory effects of activation of metabotropic glutamate receptors on GABAergic circuits in the mouse thalamus. J Neurophysiol 113:2646-52
Lam, Ying-Wan; Sherman, S Murray (2015) Functional topographic organization of the motor reticulothalamic pathway. J Neurophysiol 113:3090-7
Petrof, Iraklis; Viaene, Angela N; Sherman, S Murray (2015) Properties of the primary somatosensory cortex projection to the primary motor cortex in the mouse. J Neurophysiol 113:2400-7
Mitchell, Anna S; Sherman, S Murray; Sommer, Marc A et al. (2014) Advances in understanding mechanisms of thalamic relays in cognition and behavior. J Neurosci 34:15340-6
Sherman, S Murray (2014) The function of metabotropic glutamate receptors in thalamus and cortex. Neuroscientist 20:136-49
Liu, Tingting; Petrof, Iraklis; Sherman, S Murray (2014) Modulatory effects of activation of metabotropic glutamate receptors on GABAergic circuits in the mouse cortex. J Neurophysiol 111:2287-97
Lam, Y-W; Sherman, S M (2013) Activation of both Group I and Group II metabotropic glutamatergic receptors suppress retinogeniculate transmission. Neuroscience 242:78-84
Viaene, Angela N; Petrof, Iraklis; Sherman, S Murray (2013) Activation requirements for metabotropic glutamate receptors. Neurosci Lett 541:67-72
De Pasquale, Roberto; Sherman, S Murray (2013) A modulatory effect of the feedback from higher visual areas to V1 in the mouse. J Neurophysiol 109:2618-31

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