# Trpc5-activated neural circuits and maternal behavior

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $524,037

## Abstract

PROJECT SUMMARY
Parental behavior is the hallmark feature of all mammals, and is critical to the health of both parents and
offspring. In the majority of mammals, since only the female can lactate, it is the mother who provides maternal
care and protection of the young. Inadequate maternal care can adversely influence the development of the
offspring and impair their health in adulthood. However, the neurobiological mechanisms for the regulation of
maternal behavior remain to be fully understood. In women who exhibit impaired bonding with their infants, we
identified several loss-of-function mutations in the TRPC5 gene, which encodes the TRPC5 ion channel, a
transient receptor potential channel that conducts calcium inward currents. We used the CRISPR-Cas9
approach to generate a knock-in mouse line that mimics one such human mutation, Trpc5K34del, and found that
this mutation causes severe impairments in a wide range of maternal behaviors in mouse dams, including
ignoring pups, reduced nursing/crouching, inefficient retrieval, disrupting nests, and impaired prolactin release
upon suckling. These findings demonstrate that intact Trpc5 function is required for normal maternal behavior,
but the neurobiological mechanisms for its effect remain unclear. One objective is to test a hypothesis that
Trpc5 maintains maternal behavior via activating oxytocin neurons in the paraventricular nucleus of the
hypothalamus, which have been implicated in maternal behavior and mother-infant bonding. The second
objective is to test whether Trpc5 acts upon dopamine neurons in the substantia nigra to provide a redundant or
complementary mechanism to regulate maternal behavior. Finally, we will evaluate whether a Trpc5 activator
can ameliorate impaired maternal behavior in wild-type dams induced by psychological stress. Our work,
combining human genetic and mouse genetic experiments, has provided evidence to identify a novel molecular
basis underlying normal maternal behavior. As a logical extension of this initial and exciting discovery, we will
continue to unravel the neurobiological mechanisms by which Trpc5 maintains normal maternal behavior during
the postpartum period and will provide pre-clinical evidence to identify Trpc5 as a potential target improve
maternal care.

## Key facts

- **NIH application ID:** 10982093
- **Project number:** 1R01HD114146-01A1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** YONG XU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $524,037
- **Award type:** 1
- **Project period:** 2024-09-12 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10982093

## Citation

> US National Institutes of Health, RePORTER application 10982093, Trpc5-activated neural circuits and maternal behavior (1R01HD114146-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10982093. Licensed CC0.

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