Cortical circuits are composed of a complex network of many neuron types. Their function is dependent on how neurons are interconnected, how the connections function, and how the information delivered to individual neurons is integrated within the postsynaptic dendritic arbor. Despite extensive knowledge of the basic blueprint of cortical circuits, detailed knowledge about precisely which cell types are connected and how the multitude of connections onto a single neuron interacts is limited. The studies proposed here will reveal the laminar and fine-scale specificities of functional excitatory and inhibitory inputs to specific types of inhibitory neurons in the cerebral cortex. A novel laser scanning photostimulation method will be used to stimulate neurons that might make connections to neurons of interest, while recording electrical responses in those neurons to determine whether connections are present. With photostimulation it is possible to stimulate hundreds of sites to """"""""map"""""""" the sources of functional input to a single neuron. Combining this method with paired intracellular recordings and cross-correlation analyses of postsynaptic currents allows identification of shared inputs on a fine scale. Results from these studies will reveal similarities and differences in the input to different types of inhibitory neurons. Interactions between excitatory and inhibitory inputs will be tested by combining photostimulation based mapping of input patterns with stimulation of a single inhibitory neuron that is connected to an excitatory neuron of interest. This will directly test the ability of inhibition to shape the sources of excitation to a single neuron. Relevance: Understanding the detailed organization of cortical circuits involving specific inhibitory neuron types is necessary to obtain a mechanistic understanding of the function of the cerebral cortex. Understanding the specific roles of inhibitory neurons in cortical function has important implications for human health, as these cell types and their activities are implicated in the cortical mechanisms that regulate attention and their disruption is implicated in schizophrenia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH063912-09
Application #
7668569
Study Section
Cognitive Neuroscience Study Section (COG)
Program Officer
Vicentic, Aleksandra
Project Start
2001-08-15
Project End
2011-07-31
Budget Start
2009-08-01
Budget End
2010-07-31
Support Year
9
Fiscal Year
2009
Total Cost
$395,137
Indirect Cost
Name
Salk Institute for Biological Studies
Department
Type
DUNS #
078731668
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Luo, Liqun; Callaway, Edward M; Svoboda, Karel (2018) Genetic Dissection of Neural Circuits: A Decade of Progress. Neuron 98:865
Luo, Liqun; Callaway, Edward M; Svoboda, Karel (2018) Genetic Dissection of Neural Circuits: A Decade of Progress. Neuron 98:256-281
Juavinett, Ashley L; Nauhaus, Ian; Garrett, Marina E et al. (2017) Automated identification of mouse visual areas with intrinsic signal imaging. Nat Protoc 12:32-43
Tian, Ju; Huang, Ryan; Cohen, Jeremiah Y et al. (2016) Distributed and Mixed Information in Monosynaptic Inputs to Dopamine Neurons. Neuron 91:1374-1389
Faget, Lauren; Osakada, Fumitaka; Duan, Jinyi et al. (2016) Afferent Inputs to Neurotransmitter-Defined Cell Types in the Ventral Tegmental Area. Cell Rep 15:2796-808
Dimidschstein, Jordane; Chen, Qian; Tremblay, Robin et al. (2016) A viral strategy for targeting and manipulating interneurons across vertebrate species. Nat Neurosci 19:1743-1749
Smith, Jared B; Klug, Jason R; Ross, Danica L et al. (2016) Genetic-Based Dissection Unveils the Inputs and Outputs of Striatal Patch and Matrix Compartments. Neuron 91:1069-1084
Kim, Euiseok J; Jacobs, Matthew W; Ito-Cole, Tony et al. (2016) Improved Monosynaptic Neural Circuit Tracing Using Engineered Rabies Virus Glycoproteins. Cell Rep 15:692-699
Hasenstaub, Andrea; Otte, Stephani; Callaway, Edward (2016) Cell Type-Specific Control of Spike Timing by Gamma-Band Oscillatory Inhibition. Cereb Cortex 26:797-806
Wall, Nicholas R; De La Parra, Mauricio; Sorokin, Jordan M et al. (2016) Brain-Wide Maps of Synaptic Input to Cortical Interneurons. J Neurosci 36:4000-9

Showing the most recent 10 out of 55 publications