# Cerebellar-Cerebro Cortical Circuits in Social Behaviors

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $754,455

## Abstract

Project Summary
Recent studies have pointed to roles for the cerebellum beyond its canonical roles in motor coordination, with
evidence pointing to prominent roles in the regulation of non-motor behaviors and parallel evidence for the
contribution of cerebellar dysfunction to numerous conditions marked by non-motor challenges throughout
development1-5. Indeed, our lab has shown that cerebellar function is necessary for social behaviors and for
behavioral flexibility6. During the course of our previously funded grant period, we have published multiple
studies delineating the presence of critical periods in cerebellar-regulated behaviors, demonstrated a key role
for cerebellar CrusI in the regulation of social and repetitive behaviors, and demonstrated an important
anatomic circuit between this region and the mPFC in the regulation of these behaviors7-10. Importantly, we
also demonstrated that modulation of this circuit is sufficient to improve behaviors in a cerebellar-specific
neurodevelopmental model of tuberous sclerosis complex (TSC). However, important questions remain,
including whether this circuit has more generalizable importance in models beyond TSC and whether circuit
modulation might be sufficient to benefit, not just cerebellar-specific models, but also global, constitutive
human disease-relevant models. Moreover, although we have shown that these circuits are necessary for
proper performance of these social behaviors, how this circuit communicates and actually contributes to social
behaviors remains unknown.
In these proposed studies, we hypothesize and show preliminary data to support that these circuits are
relevant to both cerebellar-specific and global neurodevelopmental models; that neuronal activity within the
cerebellar CrusI-mPFC circuit processes social behaviors; that this communication is necessary for proper
social behavior; that disruptions of the mPFC or CrusI impairs this communication; and that social behaviors
improve upon improvement of this communication. To evaluate these hypotheses further, we propose the
following specific aims:
Specific Aim1. Delineate CrusI-mPFC circuit contribution to global/constitutive Cntnap2 mutant mice
Specific Aim2. Delineate CrusI-mPFC communication during social behaviors
Specific Aim3. Delineate integrity of CrusI-mPFC communication in cerebellar (PC-Tsc1) and
constitutive (Cntnap2) mutant mice and evaluate impact of CrusI modulation on this communication
In summary, this work will both delineate basic mechanisms underlying the cerebellar and mPFC circuit
contributions to social behaviors while also providing a pre-clinical foundation for understanding the impact of
circuit-based neuromodulation on these behaviors.

## Key facts

- **NIH application ID:** 10905554
- **Project number:** 2R01MH116882-06A1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Peter T. Tsai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $754,455
- **Award type:** 2
- **Project period:** 2019-01-01 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10905554

## Citation

> US National Institutes of Health, RePORTER application 10905554, Cerebellar-Cerebro Cortical Circuits in Social Behaviors (2R01MH116882-06A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10905554. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*