# Neurodevelopmental function of Beta1-integrin-mediated signaling events in the prefrontal cortex

> **NIH NIH F30** · EMORY UNIVERSITY · 2022 · $51,752

## Abstract

PROJECT SUMMARY:
 Adolescence is characterized by massive synaptic pruning and structural stabilization in the prefrontal
cortex (PFC). Given that ~50% of “adult” mental health disorders initially present during adolescence,
investigating factors mediating this dramatic structural change could inform disease vulnerabilities or etiologies.
 Genome-wide association studies implicate ITGB1, the gene encoding β1-integrin, in disorders such as
schizophrenia. In hippocampal CA1, stimulation of β1-integrin by extracellular matrix proteins stabilizes
dendrites and synapses starting in adolescence. We recently observed that selective reduction of Itgb1 in the
medial PFC (mPFC) has developmentally-selective consequences also, with adolescent-onset knockdown
causing anhedonic-like and risk-taking behaviors. Meanwhile, adult-onset knockdown has no such effects.
Given that the mPFC undergoes structural remodeling during adolescence – and is dysregulated in psychiatric
illnesses – clarifying the role of β1-integrin in mPFC development may provide insight into disease etiology. I
hypothesize that β1-integrin is necessary for the structural stabilization – referring here to the process
by which dendritic spines are retained and escape pruning – of excitatory mPFC neurons throughout
adolescence, and that this stability is necessary for the proper development of mPFC-regulated
behaviors.
 My first aim investigates the impact of β1-integrin on mPFC neurodevelopment and function. I will
selectively reduce neuronal Itgb1 in the mPFC (prelimbic subregion) of pre-adolescent mice. I will then image
layer V neurons – which receive input from subcortical regions involved in mPFC-dependent decision making
and mood regulation – throughout adolescence and reconstruct dendritic spines in 3D to delineate
developmental trajectories. I will next selectively reduce Itgb1 in layer V neurons and identify consequences in
sensorimotor gating, social interaction and recognition, and goal-directed decision making. I hypothesize that
Itgb1 deficiency will cause dendritic spine loss on layer V neurons, triggering behavioral abnormalities.
 Neuronal β1-integrin signaling partners include Abl2/Arg kinase, cortactin, and ROCK2, which regulate
actin polymerization. In my second aim, I will pharmacologically stimulate or inhibit (as appropriate) each of
these factors during a key period of mPFC development, vs. when dendritic spine densities are relatively stable
by comparison. I hypothesize that some or all of these pharmacomanipulations, when administered during this
key period, will correct the behavioral abnormalities observed in Itgb1-deficient mice.
 Impact: The function of β1-integrin in the mPFC is unknown, despite β1-integrin linkage with
neuropsychiatric disease and neurodevelopmental processes in other brain regions. Understanding the
neurobehavioral functions of β1-integrin in the adolescent mPFC may provide insight into novel therapeutic
approaches to neurodevelopmental disorders...

## Key facts

- **NIH application ID:** 10400669
- **Project number:** 5F30MH117878-04
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Henry W. Kietzman
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $51,752
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10400669

## Citation

> US National Institutes of Health, RePORTER application 10400669, Neurodevelopmental function of Beta1-integrin-mediated signaling events in the prefrontal cortex (5F30MH117878-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10400669. Licensed CC0.

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