# Cortical assembly formation through excitatory/inhibitory circuit plasticity

> **NIH NIH RF1** · UNIVERSITY OF CHICAGO · 2023 · $2,078,335

## Abstract

Cortical assembly formation through excitatory/inhibitory circuit plasticity.
Project Summary
Throughout the brain, sensory information is thought to be represented by the joint activity of neurons that form
functionally connected assemblies. A long-standing premise is that assemblies are formed during sensory learn-
ing by strengthening the excitatory connections between co-active neurons. However, the role of inhibition in
this process has yet to be fully elucidated. In this proposal, we will investigate the inhibitory and disinhibitory
circuits that underlie the formation, stabilization and competition between neural assemblies. However, the con-
tributions of specific interneuron classes to these processes is unknown. We have developed a theoretical model
of assembly formation that incorporates data driven inhibitory synaptic plasticity rules for Parvalbumin (PV) and
Somatostatin (SOM) expressing interneurons. Two key predictions arise from this model. First, PV interneu-
rons provide inhibition that scales with excitation to stabilize neural assemblies. And second, SOM interneurons
mediate competition between assemblies. In this proposal, we aim to experimentally test these predictions. In
the olfactory cortex, we have found that odor discrimination training promotes assembly formation in response
to rewarded odors but not unrewarded odors. In addition, we find that inhibition scales with excitation in the
rewarded assembly. Thus, the olfactory cortex provides an ideal substrate to test predictions about the specific
roles of PV and SOM neurons in assembly competition and stabilization. In Aim 1, we investigate the role of
PV interneurons in maintaining excitation and inhibition balance and stabilizing rewarded assemblies. In
Aim 2, we investigate the role for SOM interneurons in mediating inter-assembly competition. Finally, we
have shown that a disinhibitory circuit mediated by vasoactive intestinal peptide (VIP) interneurons, gates recur-
rent excitatory plasticity onto pyramidal neurons. This suggests an intriguing hypothesis that VIP interneurons
inhibit SOM interneurons to promote the specific formation of the rewarded assembly. In Aim 3, we will use a
combined theoretical and experimental approach to investigate the role of VIP-cell mediated disinhibition
in gating assembly formation.
 The studies outlined in this proposal take a comprehensive approach to investigating the synaptic and circuit
mechanisms that underlie assembly activity in the cortex. We focus on circuit motifs that are found in all cortices
and we expect our findings will have broad impact across brain areas. Our findings will illuminate the important
roles inhibitory and disinhibitory circuits play in assembly dynamics during sensory-guided behavior.

## Key facts

- **NIH application ID:** 10729689
- **Project number:** 1RF1NS133598-01
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Brent D. Doiron
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $2,078,335
- **Award type:** 1
- **Project period:** 2023-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10729689

## Citation

> US National Institutes of Health, RePORTER application 10729689, Cortical assembly formation through excitatory/inhibitory circuit plasticity (1RF1NS133598-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10729689. Licensed CC0.

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