Cortical activity is tightly regulated to support adaptive behavior, but the mechanisms underlying this regulation are unclear. In this project, we will investigate how cortical activity is regulated in vivo, directly at the site of synaptic input Dendrites actively process synaptic input using voltage-gated ion channels and NMDA receptors. We recently showed that these mechanisms support dendritic spiking in awake mice. These dendritic spikes propagate to the soma as depolarizations that can trigger conventional axonal spikes, and thus represent a layer of computational processing that contributes to neuronal selectivity. A recently elucidated circuit motif involving neuromodulation and dendrite-targeting interneurons could play a key role in regulating dendritic spiking during sensory processing and behavior. Here, we use dendritic patch clamp recordings, optogenetics, and new multiphoton imaging technology to interrogate this circuit motif, its effects on dendritic spiking, and its activity during sensory processing and behavior. Since dendritic spiking is an essential component of synaptic integration in cortical circuitry, and dysfunctional synaptic integration is implicated in complex psychiatric and neurological disorders, results from this project can eventually contribute to new therapeutic strategies.

Public Health Relevance

Many disorders of brain function result from altered cortical circuitry. It is difficult to address these diseases without a more sophisticated understanding of its functional principles. The proposed studies will elucidate mechanisms of cortical activity modulation. The results will provide cellular and circuit-level insights into mechanisms that regulate cortical circuitry during behavior, and can eventually contribute to understanding pathological brain states.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS091335-03
Application #
9231511
Study Section
Synapses, Cytoskeleton and Trafficking Study Section (SYN)
Program Officer
Stewart, Randall R
Project Start
2015-04-01
Project End
2020-03-31
Budget Start
2017-04-01
Budget End
2018-03-31
Support Year
3
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Physiology
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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Stirman, Jeffrey N; Smith, Ikuko T; Kudenov, Michael W et al. (2016) Wide field-of-view, multi-region, two-photon imaging of neuronal activity in the mammalian brain. Nat Biotechnol 34:857-62