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Updated: Jul 29, 2026

Extinction Training During the Reconsolidation Window Prevents Recovery of Fear
Published on: August 24, 2012
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.
Abstract:
Female rats exposed to fear extinction during the proestrus and estrus phases (Pro/Est) or following estradiol administration in ovariectomized females show enhanced extinction memory and reduced fear relapse relative to males and females extinguished during the metestrus and diestrus phases (Met/Di). In Pro/Est females, this effect requires activity of the substantia nigra-to-dorsolateral striatum (SN-DLS) dopamine (DA) pathway during extinction. Although elevated ovarian hormones can enhance SN-DLS DA activity, it remains unclear whether estrous phase also influences activity of catecholaminergic neurons in regions beyond the SN during extinction. Furthermore, how the nigrostriatal pathway interacts with traditional extinction networks during extinction has not yet been investigated. To address these questions, we examined sex- and estrous phase-dependent differences in neural activation and functional connectivity during extinction across a distributed network including midbrain catecholaminergic regions, traditional fear extinction networks, and striatal subregions. During extinction, Pro/Est females froze less than males and Met/Di females, exhibited less cFos in the prelimbic cortex and cingulate gyrus compared to males, had greater cFos in the medial amygdala relative to males, and displayed greater cFos within ventral tegmental area DA neurons compared to males and Met/Di females. Furthermore, functional connectivity during extinction was highest in Pro/Est females, with the DLS identified as a hub, indicating high influence over network connectivity. These findings provide new insight into how sex and estrous phase influence extinction processing and suggest the DLS may be a key region influencing extinction learning in Pro/Est females.
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