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Estradiol shifts interactions between the infralimbic cortex and central amygdala to enhance fear extinction memory in female rats.
J Neurosci Res. 2017 01 02; 95(1-2):163-175.JN

Abstract

There is growing evidence that estradiol (E2) enhances fear extinction memory consolidation. However, it is unclear how E2 influences the nodes of the fear extinction network to enhance extinction memory. This study begins to delineate the neural circuits underlying the influence of E2 on fear extinction acquisition and consolidation in female rats. After fear conditioning (day 1), naturally cycling female rats underwent extinction learning (day 2) in a low-E2 state, receiving a systemic administration of either E2 or vehicle prior to extinction training. Extinction memory recall was then tested 24 hr later (day 3). We measured immediate early gene c-fos expression within the extinction network during fear extinction learning and extinction recall. During extinction learning, E2 treatment increased centrolateral amygdala c-fos activity and reduced lateral amygdala activity relative to vehicle. During extinction recall, E2-treated rats exhibited reduced c-fos expression in the centromedial amygdala. There were no group differences in c-fos expression within the medial prefrontal cortex or dorsal hippocampus. Examining c-fos ratios with the infralimbic cortex (IL) revealed that, despite the lack of group differences within the IL, E2 treatment induced greater IL activity relative to both prelimbic cortex and central amygdala (CeA) activity during extinction memory recall. Only the relationship between IL and CeA activity positively correlated with extinction retention. In conclusion, E2 appears to modify interactions between the IL and the CeA in females, shifting from stronger amygdalar modulation of fear during extinction learning to stronger IL control during extinction recall. © 2016 Wiley Periodicals, Inc.

Authors+Show Affiliations

Department of Psychiatry, Massachusetts General Hospital, Charlestown, Massachusetts. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.Department of Psychiatry, Massachusetts General Hospital, Charlestown, Massachusetts.Department of Psychiatry, Massachusetts General Hospital, Charlestown, Massachusetts. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.Department of Psychiatry, Massachusetts General Hospital, Charlestown, Massachusetts.Department of Psychiatry, Massachusetts General Hospital, Charlestown, Massachusetts. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.Department of Psychiatry, Massachusetts General Hospital, Charlestown, Massachusetts. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

27870439

Citation

Maeng, Lisa Y., et al. "Estradiol Shifts Interactions Between the Infralimbic Cortex and Central Amygdala to Enhance Fear Extinction Memory in Female Rats." Journal of Neuroscience Research, vol. 95, no. 1-2, 2017, pp. 163-175.
Maeng LY, Cover KK, Taha MB, et al. Estradiol shifts interactions between the infralimbic cortex and central amygdala to enhance fear extinction memory in female rats. J Neurosci Res. 2017;95(1-2):163-175.
Maeng, L. Y., Cover, K. K., Taha, M. B., Landau, A. J., Milad, M. R., & Lebrón-Milad, K. (2017). Estradiol shifts interactions between the infralimbic cortex and central amygdala to enhance fear extinction memory in female rats. Journal of Neuroscience Research, 95(1-2), 163-175. https://doi.org/10.1002/jnr.23826
Maeng LY, et al. Estradiol Shifts Interactions Between the Infralimbic Cortex and Central Amygdala to Enhance Fear Extinction Memory in Female Rats. J Neurosci Res. 2017 01 2;95(1-2):163-175. PubMed PMID: 27870439.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Estradiol shifts interactions between the infralimbic cortex and central amygdala to enhance fear extinction memory in female rats. AU - Maeng,Lisa Y, AU - Cover,Kara K, AU - Taha,Mohamad B, AU - Landau,Aaron J, AU - Milad,Mohammed R, AU - Lebrón-Milad,Kelimer, PY - 2016/03/31/received PY - 2016/05/27/revised PY - 2016/06/20/accepted PY - 2016/11/22/entrez PY - 2016/11/22/pubmed PY - 2017/11/14/medline KW - PTSD KW - anxiety KW - c-fos KW - central amygdala KW - centromedial amygdala KW - estradiol KW - estrous cycle KW - fear KW - fear extinction KW - female KW - infralimbic cortex KW - sex differences KW - ventromedial prefrontal cortex SP - 163 EP - 175 JF - Journal of neuroscience research JO - J Neurosci Res VL - 95 IS - 1-2 N2 - There is growing evidence that estradiol (E2) enhances fear extinction memory consolidation. However, it is unclear how E2 influences the nodes of the fear extinction network to enhance extinction memory. This study begins to delineate the neural circuits underlying the influence of E2 on fear extinction acquisition and consolidation in female rats. After fear conditioning (day 1), naturally cycling female rats underwent extinction learning (day 2) in a low-E2 state, receiving a systemic administration of either E2 or vehicle prior to extinction training. Extinction memory recall was then tested 24 hr later (day 3). We measured immediate early gene c-fos expression within the extinction network during fear extinction learning and extinction recall. During extinction learning, E2 treatment increased centrolateral amygdala c-fos activity and reduced lateral amygdala activity relative to vehicle. During extinction recall, E2-treated rats exhibited reduced c-fos expression in the centromedial amygdala. There were no group differences in c-fos expression within the medial prefrontal cortex or dorsal hippocampus. Examining c-fos ratios with the infralimbic cortex (IL) revealed that, despite the lack of group differences within the IL, E2 treatment induced greater IL activity relative to both prelimbic cortex and central amygdala (CeA) activity during extinction memory recall. Only the relationship between IL and CeA activity positively correlated with extinction retention. In conclusion, E2 appears to modify interactions between the IL and the CeA in females, shifting from stronger amygdalar modulation of fear during extinction learning to stronger IL control during extinction recall. © 2016 Wiley Periodicals, Inc. SN - 1097-4547 UR - https://www.unboundmedicine.com/medline/citation/27870439/Estradiol_shifts_interactions_between_the_infralimbic_cortex_and_central_amygdala_to_enhance_fear_extinction_memory_in_female_rats_ DB - PRIME DP - Unbound Medicine ER -