# Integration of Experience-Induced Gene Expression and Circuit Functions

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $403,711

## Abstract

Multi-PI: Xinyu Zhao, Meyer Jackson, University of Wisconsin-Madison.
Title: Integration of Experience-Induced Gene Expression and Circuit Functions
Understanding the complex relationships between cells, gene networks, neural circuits, and behavior requires
techniques that can probe the molecular makeup of distinct types of neurons, evaluate their properties, and test
their roles in higher level functions. Genes expressed within specific populations of neurons determine their
electrical properties and these properties together with their synaptic connectivity collectively shape the electrical
activity of neural circuits. This is especially well illustrated by a population of neurons defined by expression of
the Ca2+ binding protein parvalbumin (PV). PV interneurons (PVIs) are sparsely distributed, fast-spiking cells that
provide feedback and feedforward inhibition to principal neurons. One of the most well-defined network functions
of PVIs is in the coordination of neuronal networks and their associated oscillations. PVIs entrain cortical
networks to drive gamma oscillations (30-100 Hz) and control their frequency and strength. PVI-mediated
gamma oscillations are known to have important roles in sensory processing, attention, working memory, and
cognition. However, the gene networks that control PVI functions and their impact on gamma oscillations remain
unclear. PVIs are readily modified by environmental conditions and experience. PV immunoreactivity increases
after exploration of a novel environment, rearing under environmental enrichment (EE), and voluntary running
(VR). These changes occur in brain regions associated with cognition, including hippocampus, prefrontal cortex,
and amygdala. The molecular mechanisms underlying PVI changes during behavioral adaptation remain
unknown. Although studies suggest that behavioral adaptions affect gamma oscillations, a role for PVIs in the
link between behavioral adaption and gamma oscillations has not been established. This application takes a
multidisciplinary approach to address the fundamental question of how PVIs contribute to behavioral adaptations.
Our overarching hypothesis is that changes in gene expression that modify the cellular properties of PVIs will
alter network oscillations, enabling PVIs to serve as a critical hub in behavioral adaptations. We will determine
whether behavioral adaptation mobilizes networks of genes in PVIs, and assess the contributions of these
networks to PVI physiology and gamma oscillations. This project combines the unique expertise of co-PIs Zhao
(genetic regulation of neurodevelopment) and Jackson (neurophysiology and neural circuits) and co-Is Roy
(system biology and machine learning) and Rosenberg (computational and system neuroscience). By integrating
experimental data with gene network analysis and computational modeling of multicellular networks, this work
will reveal how changes in molecular/cellular properties impact the emergent properties of neural circui...

## Key facts

- **NIH application ID:** 9897551
- **Project number:** 5R01NS105200-03
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** MEYER B. JACKSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $403,711
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9897551

## Citation

> US National Institutes of Health, RePORTER application 9897551, Integration of Experience-Induced Gene Expression and Circuit Functions (5R01NS105200-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9897551. Licensed CC0.

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