# Maintenance of excitatory/inhibitory synapse balance by ciliary signaling

> **NIH NIH R21** · BRANDEIS UNIVERSITY · 2020 · $203,125

## Abstract

PROJECT SUMMARY
 Primary cilia are sensory organelles that are now known to be present on nearly every neuron type
in the mammalian central nervous system. In the developing nervous system, cilia are essential for
progenitor proliferation, neuronal migration, and the establishment of synaptic connectivity. However,
although cilia are also present on mature neurons, their roles in the postnatal brain are poorly understood.
Intriguingly, cilia concentrate neuropeptide and amine receptors, and cilia dysfunction has been linked with
multiple neuropsychiatric diseases, suggesting that cilia-dependent neuromodulator signaling may be
critical for the maintenance and plasticity of neural circuits. The overall goal of this exploratory R21 is to
investigate the role of ciliary signaling in the acute modulation of excitatory synapse formation and function
in the postnatal brain.
 In preliminary experiments, we have found that acute disruption of cilia in postnatal cortical neurons
increases excitatory synapse number and strength. Consistent with this finding, spontaneous neuronal firing
rates (driven by synaptic input) are also increased indicating a disruption of excitation/inhibition (E/I)
balance. Since E/I imbalance contributes to multiple neuropsychiatric and metabolic disorders, our results
raise the novel and exciting possibility that ciliary signaling is essential for generating and maintaining
correct E/I balance in multiple postnatal circuits. We will take advantage of the complementary expertise of
the co-PIs (Sengupta – cilia biology, Turrigiano – synaptic physiology) to:
 Aim 1. Establish a role for ciliary signaling in the regulation of E/I balance and circuit excitability.
 Aim 2. Explore the mechanisms by which ciliary signaling modulates synaptic properties.
 Results from this work have the potential to open up new avenues for understanding how correct E/I
balance is dynamically maintained in the postnatal brain, and provide insights into how cilia dysfunction
contributes to the regulation of mental health.

## Key facts

- **NIH application ID:** 9954157
- **Project number:** 5R21MH118464-02
- **Recipient organization:** BRANDEIS UNIVERSITY
- **Principal Investigator:** Piali Sengupta
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $203,125
- **Award type:** 5
- **Project period:** 2019-06-13 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9954157

## Citation

> US National Institutes of Health, RePORTER application 9954157, Maintenance of excitatory/inhibitory synapse balance by ciliary signaling (5R21MH118464-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9954157. Licensed CC0.

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