# On circuit mechanisms of reward behaviors  after early-life adversity

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2023 · $610,182

## Abstract

SUMMARY
 Early-life adversity (ELA) is associated with vulnerability to mental illnesses that involve disruption of
the brain’s reward circuits. These vulnerabilities may manifest as anhedonia, a reduction in reward desire or
pleasure that is core feature of major depression. However, whether the association of ELA with anhedonia is
causal is difficult to establish in humans, and mechanisms underlying this relationship are not understood. Our
well-characterized rodent ELA model reliably leads to reward-circuit disruptions in a sex-dependent manner,
yet the circuit nodes and pathways that are most affected remain unclear.
 In searching for ELA-sensitive reward-circuit components, we discovered and are characterizing a
novel projection from basolateral amygdala (BLA) to nucleus accumbens (NAc) that expresses the
neuropeptide corticotropin releasing hormone (CRH). Neurons expressing CRH are often stress-sensitive, and
our preliminary data suggest this is also the case for the novel CRH+BLA-NAc pathway. Building on these
robust data, we will determine the functional roles of the projection in mice and test the hypothesis that ELA-
induced plasticity in this pathway contributes to sex-dependent effects of ELA on reward pursuit and
consumption, significantly advancing our understanding of the origins of mental illness.
 Aim 1 will test the hypothesis that the novel CRH+BLA-NAc pathway modulates reward pursuit
(motivation) and / or consumption in typically reared male and female mice, capitalizing on the temporal
resolution of optogenetics and on formal motivation tasks to probe the specific role of the projection in the
motivational vs. consummatory aspects of reward. Aim 2 will use the same technologies to determine the role
of the CRH+ BLA-NAc projection in aberrant, sex-specific reward behaviors resulting from ELA. Aim 3 will
examine the molecular and cellular mechanisms by which aberrant CRH+ BLA-NAc inputs regulate reward
behaviors: we will identify the target cells of the projection following ex vivo optogenetic activation of BLA-
origin projection fibers in the NAc, and determine the relative roles of GABA neurotransmission vs CRH
receptor activation in the effects of projection stimulation on reward behaviors in male and female mice.

## Key facts

- **NIH application ID:** 10735759
- **Project number:** 1R01MH132680-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Tallie Z. Baram
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $610,182
- **Award type:** 1
- **Project period:** 2023-08-01 → 2028-07-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10735759

## Citation

> US National Institutes of Health, RePORTER application 10735759, On circuit mechanisms of reward behaviors  after early-life adversity (1R01MH132680-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10735759. Licensed CC0.

---

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