# The roles of delta-catenin in social behavior

> **NIH NIH R01** · COLORADO STATE UNIVERSITY · 2024 · $32,821

## Abstract

Many species depend on social activity to thrive, and social impairment is a fundamental symptom of several
mental diseases. According to research, synaptic signals and activity can control social behavior. Yet, it is still
unclear how synapse control and social behavior are related. δ-catenin functions as an anchor for the
glutamatergic AMPA receptor (AMPARs) to regulate synaptic activity in excitatory synapses. Several families
with autism have been identified to have mutations in the δ-catenin gene, which results in a loss of δ-catenin
functions at excitatory synapses and is thought to be the etiology of autism in people. Recent studies, including
our own, suggest that the loss of δ-catenin functions significantly decreases cortical neurons' inhibition to
increase excitation. Our new data further reveal that δ-catenin deficiency disrupts social behavior in mice. These
new findings strongly support the scientific premise that δ-catenin is critical for glutamatergic synaptic activity
and social behavior. Nonetheless, the δ-catenin-mediated link of synaptic, cellular, and neural substrates to
social behavior is understudied. The significance of the current proposal is thus predicated on filling this gap.
Postsynaptic glutamatergic activity in excitatory and inhibitory cells in the medial prefrontal cortex (mPFC)
regulates cellular excitation and inhibition to control prefrontal rhythmic activity patterns, which is essential in the
control of social behavior in humans and animals. However prior research on the neural basis of social behavior
has mostly concentrated on top-down mPFC projections to various subcortical regions. Hence, in these earlier
studies, glutamatergic inputs to prefrontal neurons were mainly disregarded. Therefore, it is unclear how the
postsynaptic glutamatergic activity of prefrontal cells relates to social behavior. Research suggests that
parvalbumin-positive (PV+) inhibitory interneurons in the mPFC receive direct glutamatergic inputs from multiple
subcortical regions to provide feedforward inhibition onto prefrontal pyramidal neurons and control network
activity. This is important for the regulation of social behavior. Our preliminary data suggest that δ-catenin
deficiency impairs prefrontal neural activity at cellular and network levels to induce social deficits. Therefore,
existing data and our new findings lead us to hypothesize that δ-catenin is important for glutamatergic activity
in PV+ inhibitory interneurons to provide feedforward inhibition onto pyramidal neurons in the mPFC, which
regulates prefrontal activity at the cellular and network levels to ensure normal social behavior. We will employ
two new mouse models of δ-catenin deficiency - δ-catenin KO mice and human ASD-associated δ-catenin
glycine 34 to serine (G34S) mutant mice – to examine if δ-catenin controls pathway-specific glutamatergic activity
in PV+ interneurons and feedforward inhibition onto pyramidal neurons in the mPFC (Aim 1), to determine
whether...

## Key facts

- **NIH application ID:** 11058987
- **Project number:** 3R01MH132921-01A1S1
- **Recipient organization:** COLORADO STATE UNIVERSITY
- **Principal Investigator:** Seonil Kim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $32,821
- **Award type:** 3
- **Project period:** 2023-11-15 → 2028-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11058987

## Citation

> US National Institutes of Health, RePORTER application 11058987, The roles of delta-catenin in social behavior (3R01MH132921-01A1S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11058987. Licensed CC0.

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