# Dendritic-Targeting Cortical Interneurons and Their Role in Associative Learning

> **NIH NIH R56** · WEST VIRGINIA UNIVERSITY · 2020 · $505,234

## Abstract

PROJECT SUMMARY/ ABSTRACT
GABA-containing Inhibitory interneurons are <20% of all cortical neurons, yet are critically important for proper
cortical development and function. Dysfunction of inhibitory cortical interneurons is implicated in a wide range of
mental and neurological disorders. Inhibitory interneurons comprise several subclasses which are
distinguishable by their neurochemical content, morphology, electrophysiology and synaptic connectivity. A
prominent subclass are somatostatin-containing interneurons, which preferentially target distal dendrites of
excitatory neurons. What functions this distal inhibition performs in cortical computations, and how these
interneurons contribute to sensation, perception and behavior, is still not fully understood. The PI has previously
shown that somatostatin interneurons comprise (at least) two broad subsets which differ in their main axonal
targets: those targeting most heavily layer 4, the layer receiving “bottom-up” sensory information, and those
targeting layer 1, the layer receiving “top-down” contextual information from higher-order brain regions. The
objective of the proposed research is to develop novel genetic approaches to target these distinct subsets and
to shed light on their roles in cortical computations underlying behavior and learning. The proposed research will
test the hypothesis that layer 4- and layer 1-targeting somatostatin interneurons have diverged to modulate and
constrain the two major input systems of the cortex, and that during associative learning these two systems work
in a push-pull fashion, to shift the balance between these two pathways in favor of top-down inputs. The proposed
study will employ a novel combinatorial genetic approach with newly developed intersectional viral vectors, to
separately target each of the two subsets for electrophysiological recording, two-photon calcium imaging and
light-induced activation. Using these tools, the applicants will examine the detailed pattern of synaptic
connections between these interneuron subsets and excitatory neurons, and will monitor changes in these two
inhibitory systems as the animal learns to associate two stimuli. Achieving the aims of the proposal would be a
major advance in our understanding of how cortical circuits are organized, how they evolved and how they are
rewired during learning.

## Key facts

- **NIH application ID:** 10131294
- **Project number:** 1R56NS116604-01
- **Recipient organization:** WEST VIRGINIA UNIVERSITY
- **Principal Investigator:** ARIEL AGMON
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $505,234
- **Award type:** 1
- **Project period:** 2020-05-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10131294

## Citation

> US National Institutes of Health, RePORTER application 10131294, Dendritic-Targeting Cortical Interneurons and Their Role in Associative Learning (1R56NS116604-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10131294. Licensed CC0.

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