# Determinants of sparse activity in neocortex

> **NIH NIH R01** · CARNEGIE-MELLON UNIVERSITY · 2024 · $492,287

## Abstract

ABSTRACT
Synaptic plasticity in neocortical neurons is intimately tied to learning and memory. Decades of
research in acute brain slices have characterized the patterns of spike timing required to evoke
synaptic change in minute detail, but it remains unknown whether these conditions occur and
are sufficient to drive synaptic plasticity in the living brain. Indeed, in vivo recordings indicate
that neocortical neurons live in an environment of profound inhibition that lowers overall firing
rates and prevents plasticity. How then do cortical neurons escape this inhibition to encounter
appropriate conditions for plasticity during learning? New evidence suggests that parvalbumin
(PV) GABAergic neurons may play a dominant role in regulating cortical activity and controlling
network rewiring, particularly at the early stages of learning. Using a multiwhisker stimulus
coupled to a water reward, we have developed a paradigm for sensory association learning that
drives rapid changes in excitatory synaptic strength in mouse barrel cortex. Importantly, our
new data indicate that PV output to neocortical pyramidal neurons is markedly suppressed at
the earliest stages of sensory training. Our experiments will integrate in vivo and acute brain
slice recordings to test the hypothesis that PV neurons are a dominant regulator of sensory-
evoked activity in mouse barrel cortex. We propose that reward-related acetylcholine release
indirectly suppresses PV neural firing to depress PV output and increase sensory-evoked
activity during learning. Our experiments will identify mechanisms for cortical disinhibition that
facilitate experience-dependent synaptic plasticity in sensory cortex.

## Key facts

- **NIH application ID:** 10748370
- **Project number:** 5R01NS123711-03
- **Recipient organization:** CARNEGIE-MELLON UNIVERSITY
- **Principal Investigator:** ALISON L BARTH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $492,287
- **Award type:** 5
- **Project period:** 2022-02-15 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10748370

## Citation

> US National Institutes of Health, RePORTER application 10748370, Determinants of sparse activity in neocortex (5R01NS123711-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10748370. Licensed CC0.

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