The function of the nervous system is dependent on complex interactions between networks of neurons composed of multiple neuron types. Understanding how these networks function both in health and disease is dependent on understanding the precise connectivity between specific neurons types and their functional interactions in the intact brain. It is therefore apparent that, in order to have an adequate understanding of the nervous system, it is necessary to have detailed descriptions of neuronal connectivity with the same level of precision at which these systems operate and to selectively manipulate and measure the activity of specific cell types in the context of the normal functioning network. The research proposed here is aimed at revealing the detailed connectivity and function of specific types of inhibitory cortical neurons. Intersectional genetic methods and Cre- and Flp-driver mouse lines are used to target gene expression to specific subsets of VIP positive inhibitory cortical neurons. The direct synaptic inputs and outputs of these neurons are then determined by monosynaptic rabies tracing or by optogenetic activation and whole cell recordings in brain slices. These same cell types will be optogenetically activated in vivo to assess their impact on other cells in the intact network and in the generation of sensory receptive fields. These experiments are designed to test hypotheses about the interactions between specific neural elements and their contributions to perception, cognition, and behavior.

Public Health 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 i implicated in schizophrenia and autism.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH063912-18
Application #
9450538
Study Section
Mechanisms of Sensory, Perceptual, and Cognitive Processes Study Section (SPC)
Program Officer
Rossi, Andrew
Project Start
2001-08-15
Project End
2021-03-31
Budget Start
2018-04-01
Budget End
2019-03-31
Support Year
18
Fiscal Year
2018
Total Cost
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
Tuncdemir, Sebnem N; Wamsley, Brie; Stam, Floor J et al. (2016) Early Somatostatin Interneuron Connectivity Mediates the Maturation of Deep Layer Cortical Circuits. Neuron 89:521-35
Padmanabhan, Krishnan; Osakada, Fumitaka; Tarabrina, Anna et al. (2016) Diverse Representations of Olfactory Information in Centrifugal Feedback Projections. J Neurosci 36:7535-45
Zarrinpar, Amir; Callaway, Edward M (2016) Functional Local Input to Layer 5 Pyramidal Neurons in the Rat Visual Cortex. Cereb Cortex 26:991-1003
Xu, Chun; Krabbe, Sabine; GrĂ¼ndemann, Jan et al. (2016) Distinct Hippocampal Pathways Mediate Dissociable Roles of Context in Memory Retrieval. Cell 167:961-972.e16
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

Showing the most recent 10 out of 55 publications