# Examining the neuronal mechanisms underlying stress-accelerated habit

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $49,038

## Abstract

The brain has two strategies for behavioral control. Goal-directed actions which rely on prospective
consideration of potential outcomes and consequences, and habits, reflexive behaviors executed without
forethought of their consequences. Overreliance on habit causes maladaptive compulsive behavior that
characterizes substance use disorder and other psychiatric conditions. Stress is a major predisposing factor to
substance use disorder and can also cause an overreliance on habit. However, our understanding of the brain
mechanisms by which stress influences habits is lacking, limiting our understanding of how stress promotes
maladaptive compulsive behavior in substance use disorder. Therefore, the broad goal of this project is to reveal
the neuronal mechanisms by which stress promotes habit formation.
 Accumulating evidence suggests that the dorsomedial striatum, part of the basal ganglia, is responsible for
controlling goal-directed actions. Inhibition of the dorsomedial striatum, particularly Drd1+ direct pathway
neurons, disrupts goal-directed control, resulting in a bias toward habits. The central amygdala (CeA), a majority
inhibitory nucleus, is known to be a hub for stress-responsivity in the brain. Until recently, it was thought that the
CeA and dorsal striatum are not directly connected. However, modern tracing techniques have revealed direct
projections between these two regions, which I have found are biased towards the dorsomedial striatum.
Interestingly, in my graduate work I discovered that CeA projections to other parts of the basal ganglia convey
information about aversive stimuli. This led me to the intriguing hypothesis that amygdala-striatal projections
convey information about stress to block goal-directed actions, biasing behavior toward habits. Through the
proposed research I will reveal the mechanistic role of central amygdala-striatal projections in the context of
stress-potentiated habit formation. I will accomplish this using a multifaceted approach of cutting-edge
neuroscience techniques in mice. In Aim 1, I will apply in vivo fiber photometry imaging and optogenetic
manipulation during a sophisticated behavioral paradigm to determine the temporal dynamics and sufficiency of
central amygdala-striatal projections in controlling habits after stress. In Aim 2, I will reveal the endogenous
activity dynamics of dorsomedial Drd1+ striatal ensembles during habit formation and how this activity is altered
by stress and differs in the absence of CeA input using chemogenetics. The resulting findings will provide a
mechanistic understanding of habit formation in both the normal context and after stress exposure. This will
facilitate future work into the molecular and cellular mechanisms of this phenomenon and serve my goal of
improving treatment approaches for substance use disorder and other stress-related conditions.
 I will conduct this project in the Wassum Lab at UCLA, with the guidance of a remarkable mentoring team.
This envi...

## Key facts

- **NIH application ID:** 10463492
- **Project number:** 1F32DA056201-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Jacqueline Giovanniello
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $49,038
- **Award type:** 1
- **Project period:** 2022-04-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10463492

## Citation

> US National Institutes of Health, RePORTER application 10463492, Examining the neuronal mechanisms underlying stress-accelerated habit (1F32DA056201-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10463492. Licensed CC0.

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