We shall initially use in vitro slice preparations from the mouse brain to study thalamocortical interactions in both directions in the visual system, concentrating on cortical areas V1 and V2 and thalamic nuclei LGN and LP. We then propose to develop in vivo preparations to test hypotheses from the in vitro work. We make heavy use of optogenetics in combination with other stimulation paradigms to activate specific pathways and use both single cell recording and current source density analysis to measure responses. We are particularly interested in the role of the two distinct corticothalamic projections. One emanates from layer 6 and feeds back to the thalamic nucleus innervating that area;we hypothesize that its main function is to depress thalamocortical transmission by multiple complementary mechanisms. The other emanates from layer 5 and is organized in a feed forward fashion, innervating thalamic regions that do not innervate its cortical area;we hypothesize that this represents the initiation of a transthalamic, cortico-thalamo-cortical pathway organized in parallel with direct corticocortical projections. Finally, we shall also test the hypothesis that these dual pathways operate in a coincidence detection manner to control information flow. This could 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 visual information flow through the first few stages of cortical processing to begin to understand how pathology in these pathways leads to vision loss including defects in cognitive visual functions, such as selective attention and object recognition. This could also lead to insights into disorders such as schizophrenia, which shows deficits in the sort of corticothalamic relationships we propose to study.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY022338-02
Application #
8444407
Study Section
Special Emphasis Panel (SPC)
Program Officer
Steinmetz, Michael A
Project Start
2012-04-01
Project End
2017-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
2
Fiscal Year
2013
Total Cost
$370,500
Indirect Cost
$133,000
Name
University of Chicago
Department
Biology
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
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
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