# Sexually Dimorphic Amygdala Dysfunction in a Mouse Model of Global Cerebral Ischemia

> **NIH NIH F99** · UNIVERSITY OF COLORADO DENVER · 2024 · $41,628

## Abstract

Project Summary/Abstract
While advances in resuscitation science have improved cardiac arrest survival, we lack therapies to improve
cognitive-affective outcomes in this patient population. Our lab has previously identified cognitive dysfunction in
a mouse model of global cerebral ischemia (GCI) which has been attributed to hippocampal neurodegeneration
and impaired hippocampal plasticity. However, no study has attempted to identify amygdala dysfunction after
GCI, despite clinical evidence of emotional dysfunction, such as anxiety and Post-Traumatic Stress Disorder
(PTSD). Therefore, it is important to identify the effect that GCI has on the amygdala, the emotional center of the
brain. Our lab has a well-developed, translatable mouse model of GCI, the cardiac arrest/cardiopulmonary
resuscitation model (CA/CPR), that has been instrumental in assessing amygdala function after GCI. I have
utilized the amygdala-dependent delay-fear conditioning (DFC) paradigm to assess associative learning and
memory and have performed field excitatory post-synaptic potential (fEPSP) recordings in two circuits within the
amygdala, as measures of amygdala function. I have found a sexually dimorphic and circuit specific deficit in
amygdala function after GCI and am working toward identifying the mechanism of this dysfunction. I have found
that there is a male specific impairment in amygdala-dependent associative learning and a concomitant deficit
of long-term potentiation (LTP) in the cortical input to the basolateral amygdala. I have also found no evidence
that these deficits of amygdala function can be attributed to neurodegeneration within the amygdala. I have
verified that there are differential mechanisms of LTP induction between the two circuits and this difference has
led to the development of my hypothesis put forth in this proposal. The difference being, LTP of the cortical input
to the BLA requires functional NMDA receptors and L-type calcium channels (LTCCs), whereas the intra
amygdala circuit only requires functional NMDA receptors. Thus, I hypothesize that GCI induces dysfunction of
LTCC's within the BLA of male mice, thereby contributing to the deficits in amygdala-dependent behavior and
LTP. To assess this hypothesis, I have isolated and recorded LTCC mediated currents from BLA pyramidal
neurons. This method, while powerful, has yielded no significant difference between CA/CPR and sham animals.
However, a caveat of the method is that only somatic and peri somatic LTCCs can be measured. Therefore, to
fully evaluate my hypothesis, I have proposed more site-specific experiments that will evaluate the contribution
of LTCC's to synaptic transmission at individual distal dendritic spines. I will use two-photon calcium imaging of
individual spines in the BLA while electrically inducing LTP of the cortical input to the BLA. I will then use
pharmacology to identify the LTCC component of the calcium response and compare between sham and
CA/CPR animals.

## Key facts

- **NIH application ID:** 10931613
- **Project number:** 5F99NS135766-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Jose Jacob Vigil
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $41,628
- **Award type:** 5
- **Project period:** 2023-09-19 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10931613

## Citation

> US National Institutes of Health, RePORTER application 10931613, Sexually Dimorphic Amygdala Dysfunction in a Mouse Model of Global Cerebral Ischemia (5F99NS135766-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10931613. Licensed CC0.

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