# Circuit, cellular, and molecular plasticity in hypothalamic microcircuits underlying flexible infant-directed behavior

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2024 · $545,450

## Abstract

ABSTRACT
Human parents and non-parents show sharply distinct patterns of brain activity in response to infant cries or
laughter. How is this change in brain responses accomplished? Receiving parental care is essential for
appropriate physical, cognitive, and emotional development in infants. Failure to care for an infant predisposes
the individual to neurodevelopmental and psychiatric disorders. Caregiving behavior is mediated by neural
circuits that promote bonding with infants. Past research has primarily focused on neural mechanisms in
mothers associated with pregnancy, parturition, and lactation that facilitate parenting. However, many species
show bi-parental care, suggesting that additional mechanisms drive infant care in males. Recent studies have
identified neural circuits involved in pro- and anti-parental behavior in both males and females. In this
proposal, we aim to leverage our knowledge about these molecularly defined circuits involved in pro- and anti-
parental behavior in mice to reveal how hypothalamic circuits nodes directly interact to coordinate infant-
directed behavior across behavioral states. How does circuit activity in molecularly defined populations
correlate with infant-directed behavior? In Aim 1, we will address this question by determining the relationship
of two molecularly defined circuit nodes critical for infant-directed behavior using in vivo fiber photometry and
chemogenetic manipulations. What synaptic mechanisms underlie observed behaviorally relevant circuit
activity? In Aim 2, we will address this question using electrophysiological (whole cell recording with
optogenetic or pharmacological manipulations) techniques to dissect cell intrinsic and plasticity mechanisms
within this molecularly defined microcircuit in behaviorally phenotyped animals. These experiments are
designed to disentangle intrinsic mechanisms and plasticity induced by synaptic or neuropeptidergic effects
across behavioral states in both sexes. What molecules underlie behaviorally relevant circuit and synaptic
mechanisms? In Aim 3, we will address this question using translating ribosome affinity purification followed
by RNASeq to identify candidate genes for specific mechanisms underlying behavioral, circuit, and synaptic
effects. These genes will be validated by in situ hybridization. Together, these experiments will uncover the
common or dissociable neural circuit mechanisms underlying adaptive infant-directed behavior across sexes
and behavioral states and provide the initial electrophysiological characterization of this neuropeptidergic
hypothalamic microcircuitry. With the increased recognition of a dedicated circuit for negative infant-directed
behavior, it is critical to have a mechanistic understanding of the neurobiological and physiological interactions
among circuitry underlying pro- and anti-parental behaviors. Understanding the mechanisms for caregiving
allows us to identify key entry points for intervention to support healt...

## Key facts

- **NIH application ID:** 10980886
- **Project number:** 1R01HD113787-01A1
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Anita Autry
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $545,450
- **Award type:** 1
- **Project period:** 2024-08-08 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10980886

## Citation

> US National Institutes of Health, RePORTER application 10980886, Circuit, cellular, and molecular plasticity in hypothalamic microcircuits underlying flexible infant-directed behavior (1R01HD113787-01A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10980886. Licensed CC0.

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