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.
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.
|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|
|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|
|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|
|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|
|Petrof, Iraklis; Viaene, Angela N; Sherman, S Murray (2012) Two populations of corticothalamic and interareal corticocortical cells in the subgranular layers of the mouse primary sensory cortices. J Comp Neurol 520:1678-86|
|Viaene, Angela N; Petrof, Iraklis; Sherman, S Murray (2011) Synaptic properties of thalamic input to layers 2/3 and 4 of primary somatosensory and auditory cortices. J Neurophysiol 105:279-92|
|Viaene, Angela N; Petrof, Iraklis; Sherman, S Murray (2011) Properties of the thalamic projection from the posterior medial nucleus to primary and secondary somatosensory cortices in the mouse. Proc Natl Acad Sci U S A 108:18156-61|
|Covic, Elise N; Sherman, S Murray (2011) Synaptic properties of connections between the primary and secondary auditory cortices in mice. Cereb Cortex 21:2425-41|
|Lee, Charles C; Sherman, S Murray (2011) On the classification of pathways in the auditory midbrain, thalamus, and cortex. Hear Res 276:79-87|
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