Local Estrogen Synthesis Regulates Parallel Fiber-Purkinje Cell Neurotransmission Within the Cerebellar Cortex

Valerie L. Hedges, Gang Chen, Lei Yu, Amanda A. Krentzel, Joseph R. Starrett, Jing Ning Zhu, Piratheepan Suntharalingam, Luke Remage-Healey, Jian Jun Wang, Timothy J. Ebner, Paul G. Mermelstein

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Estrogens affect cerebellar activity and cerebellum-based behaviors. Within the adult rodent cerebellum, the best-characterized action of estradiol is to enhance glutamatergic signaling. However, the mechanisms by which estradiol promotes glutamatergic neurotransmission remain unknown. Within the mouse cerebellum, we found that estrogen receptor activation of metabotropic glutamate receptor type 1a strongly enhances neurotransmission at the parallel fiber-Purkinje cell synapse. The blockade of local estrogen synthesis within the cerebellum results in a diminution of glutamatergic neurotransmission. Correspondingly, decreased estrogen availability via gonadectomy or blockade of aromatase activity negatively affects locomotor performance. These data indicate that locally derived, and not just gonad-derived, estrogens affect cerebellar physiology and function. In addition, estrogens were found to facilitate parallel fiber-Purkinje cell synaptic transmission in both sexes. As such, the actions of estradiol to support cerebellar neurotransmission and cerebellum-based behaviors might be fundamental to understanding the normal processing of activity within the cerebellar cortex.

Original languageEnglish (US)
Pages (from-to)1328-1338
Number of pages11
Issue number3
StatePublished - Mar 1 2018

Bibliographical note

Funding Information:
Financial Support: This work was supported by the National Institute of Neurologic Disorders and Stroke (Grant NS077661 to P.G.M. and T.J.E.; Grants NS062158 and NS18338 to T.J.E.; and Grants NS066179 and NS082179 to L.R.-H.); the National Institute on Drug Abuse (Grants DA035008 and DA041808 to P.G.M.); the National Natural Science Foundation of China (Grants 31330033, 91332124, and 31461163001 to J.-J.W.; and Grants 81671107 and 31471112 to J.-N.Z.); the Specialized Research Fund for the Doctoral Program of Higher Education and Research Grants Council Earmarked Research Grants (Grant 20130091140003 to J.-J.W.); and the Jiangsu Natural Science Foundation (Grant BK2011014 to J.-J.W.).

Publisher Copyright:
Copyright © 2018 Endocrine Society.


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