Specific cell types and their connectivity are a key determinant in neural function and selectivity. Primary visual cortex (V1) is one of the largest and most complex structures in the brain and several recent technological advances have enabled more detailed probing of cell type specific relationships to connectivity for a range of V1 cell functions, including orientation selectivity, aperture tuning, contrast response functions, an gain control. Nevertheless, technical limitations remain that have largely limited these studies to transgenic mice which lack more complex organization found in higher visual species like cat and monkey. We recently developed viral strategies for accessing specific cell types and specific circuits in non-transgenic species (Liu et al., 2013, Curr Biol) opening the door for unprecedented fine scale study of structure-function relationships in highly visual mammals. For this proposal we will apply these new strategies to enable optogenetic manipulation of specific cell types and circuits in cat V1, including superficial layer inhibitory neurons (Aim 1), long-ran lateral inputs to superficial inhibitory neurons (Aim 2), and layer 5 and 6 subcortical projection neurons that directly (or indirectly) interact with superficial layer neurons (Aim 3). Specific questions that we will address include whether and how orientation selectivity and surround suppression interact and are mediated by each of these circuits. These studies will represent the most direct in vivo assessment of inhibitory neurons and underlying intra- and inter-laminar circuitry of a large, highly visual mammal, advancing our understanding of how basic visual processes arise and depend on complex cortical structure.

Public Health Relevance

Specific cell types and their connectivity are a key determinant in neural function and selectivity. Primary visual cortex (V1) is one of the largest and most complex structures in the brain, yet very little is known regarding the functional role of specific cell types and circuits, especially in non-rodent species that depend highly on vision. To address this our approach involves a number of highly innovative tools including recombinant adeno-associated viruses, cell-type specific promoters, a genetically modified and pseudo-typed rabies virus, intrinsic signal optical imaging, and optogenetics. These studies will represent the most direct in vivo assessment of inhibitory neurons and underlying intra- and inter-laminar circuitry of a large, highly visual mammal, advancing our understanding of how basic visual processes arise and depend on complex cortical structure.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY024890-04
Application #
9405548
Study Section
Mechanisms of Sensory, Perceptual, and Cognitive Processes Study Section (SPC)
Program Officer
Flanders, Martha C
Project Start
2015-01-01
Project End
2018-12-31
Budget Start
2018-01-01
Budget End
2018-12-31
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92617