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Published on: August 24, 2012
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Sex and estrous phase influence functional connectivity during fear extinction
Alyssa A Hohorst1, Jessica D Westerman2, Carolina Sanchez-Mendoza2
1University of Colorado Denver, Department of Integrative Biology, Campus Box 171, P.O. Box 173364, Denver, CO 80217-3364, United States; University of Colorado Denver, Department of Psychology, Campus Box 173, P.O. Box 173364, Denver, CO 80217-3364, United States.
Behavioural Brain Research
|January 13, 2026
Summary
Female rats show enhanced fear extinction memory during specific estrous phases, linked to dopamine pathway activity. This highlights how hormonal cycles influence fear learning and relapse prevention.
Area of Science:
- Neuroscience
- Behavioral Endocrinology
- Neurobiology of Fear
Background:
- Fear extinction memory is enhanced in female rats during proestrus/estrus (Pro/Est) compared to metestrus/diestrus (Met/Di) phases.
- This enhanced memory in Pro/Est females requires the substantia nigra-to-dorsolateral striatum (SN-DLS) dopamine (DA) pathway.
- The influence of estrous phase on broader catecholaminergic activity and network interactions during extinction remains unclear.
Purpose of the Study:
- To investigate sex- and estrous phase-dependent differences in neural activation and functional connectivity during fear extinction.
- To examine how the nigrostriatal pathway interacts with traditional fear extinction networks.
- To identify key brain regions influencing extinction learning based on hormonal status.
Main Methods:
- Examined neural activation (cFos expression) and functional connectivity during fear extinction in rats.
- Compared Pro/Est females, Met/Di females, and males across various brain regions including midbrain catecholaminergic areas, fear extinction networks, and striatal subregions.
- Analyzed differences in freezing behavior, cFos expression, and network connectivity.
Main Results:
- Pro/Est females exhibited less freezing and reduced cFos in the prelimbic cortex and cingulate gyrus compared to males.
- Pro/Est females showed greater cFos in the medial amygdala and ventral tegmental area dopamine neurons than males and Met/Di females.
- Highest functional connectivity during extinction was observed in Pro/Est females, with the DLS acting as a central hub.
Conclusions:
- Estrous phase significantly influences neural processing during fear extinction, impacting both behavior and brain activity.
- The dorsolateral striatum (DLS) plays a crucial role as a network hub in Pro/Est females, potentially mediating enhanced extinction learning.
- Findings provide novel insights into the neurobiological mechanisms underlying sex- and hormone-dependent modulation of fear extinction.
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