# Revealing the neural mechanisms of amygdala-striatal control of stress-induced habits

> **NIH NIH K99** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $116,532

## Abstract

The brain has two strategies for behavioral control. Goal-directed actions that rely on prospective
consideration of their outcomes and consequences, and habits, reflexive responses performed without
forethought of their consequences. Overreliance on habit contributes to maladaptive perseverative behavior,
which characterizes numerous psychiatric conditions, including autism. Environmental factors, like chronic
stress, and genetic alteration, can tip the balance between actions and habits. However, our knowledge of the
brain mechanisms by which these factors influence habits is lacking, limiting our understanding of maladaptive
behaviors in psychiatric conditions, and how to treat them effectively. Therefore, the broad goal of my research
is to reveal specific neuronal mechanisms that allow genes and the environment to modulate behavioral control.
 Accumulating evidence suggests the dorsomedial striatum (DMS) is central for controlling goal-directed
actions. Inhibition of the DMS, particularly Drd1+ direct pathway neurons, disrupts goal-directed control, resulting
in a bias toward habits. The basolateral amygdala (BLA) is a known hub for stress-responsivity in the brain and
projects onto DMS Drd1+ neurons. My postdoctoral work has revealed that BLA-DMS activity supports goal-
directed learning and is suppressed after chronic stress exposure. Further, I found that activation of BLA-DMS
projections in stressed animals is sufficient to restore goal-directed control. This led me to the intriguing
hypothesis that chronic stress dysregulates DMS Drd1+ control of goal-directed learning via BLA-DMS input.
Through the proposed research, I will reveal how chronic stress changes the DMS Drd1+ neuronal activity
associated with goal-directed learning, at the population and single-cell levels, and how BLA input facilitates this.
I will accomplish this using cellular resolution in vivo calcium imaging with miniscopes, combined with projection-
specific chemogenetic manipulation, in mice (Aim 1; K99). In my independent phase, I will apply these techniques
to a mouse model of 16p11.2 microdeletion, a genetic alteration associated with autism and that is known to
dysregulate striatal function. Specifically, I will examine the vulnerability to premature habits of 16p11.2 mice,
normally and after stress, and assess amygdala-striatal control, using cell-type specific in vivo calcium imaging
with miniscopes, slice electrophysiology, and projection-specific optogenetic manipulations (Aim 2; R00). My
findings will provide a mechanistic understanding of habitual control normally, after stress, and in a model of
autism-associated genetic alteration. This will facilitate future work into the molecular and cellular mechanisms
of this phenomenon and ultimately serve my goal of improving treatment approaches for psychiatric conditions.
 I will conduct my K99 training in the Wassum Lab at UCLA, with the guidance of a remarkable mentoring
team that has pioneered the open source...

## Key facts

- **NIH application ID:** 10784498
- **Project number:** 1K99MH135177-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Jacqueline Giovanniello
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $116,532
- **Award type:** 1
- **Project period:** 2023-12-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10784498

## Citation

> US National Institutes of Health, RePORTER application 10784498, Revealing the neural mechanisms of amygdala-striatal control of stress-induced habits (1K99MH135177-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10784498. Licensed CC0.

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