Estrogen receptor alpha is required in GABAergic, but not glutamatergic, neurons to masculinize behavior

Wu, Melody V., Tollkuhn, Jessica (July 2017) Estrogen receptor alpha is required in GABAergic, but not glutamatergic, neurons to masculinize behavior. Hormones and Behavior, 95. pp. 3-12. ISSN 0018-506X

URL: https://www.ncbi.nlm.nih.gov/pubmed/28734725
DOI: 10.1016/j.yhbeh.2017.07.001

Abstract

Masculinization of the altricial rodent brain is driven by estrogen signaling during a perinatal critical period. Genetic deletion of estrogen receptor alpha (Esr1/ERα) results in altered hypothalamic-pituitary-gonadal (HPG) axis signaling and a dramatic reduction of male sexual and territorial behaviors. However, the role of ERα in masculinizing distinct classes of neurons remains unexplored. We deleted ERα in excitatory or inhibitory neurons using either a Vglut2 or Vgat driver and assessed male behaviors. We find that Vglut2-Cre;Esr1lox/lox mutant males lack ERα in the ventrolateral region of the ventromedial hypothalamus (VMHvl) and posterior ventral portion of the medial amygdala (MePV). These mutants recapitulate the increased serum testosterone levels seen with constitutive ERα deletion, but have none of the behavioral deficits. In contrast, Vgat-Cre;Esr1lox/lox males with substantial ERα deletion in inhibitory neurons, including those of the principal nucleus of the bed nucleus of the stria terminalis (BNSTpr), posterior dorsal MeA (MePD), and medial preoptic area (MPOA) have normal testosterone levels, but display alterations in mating and territorial behaviors. These mutants also show dysmasculinized expression of androgen receptor (AR) and estrogen receptor beta (Esr2). Our results demonstrate that ERα masculinizes GABAergic neurons that gate the display of male-typical behaviors.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > small molecules > GABAergic
bioinformatics > genomics and proteomics > small molecules > estrogen
bioinformatics > genomics and proteomics > small molecules > Glutamate
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
CSHL Authors:
Communities: CSHL labs > Tollkuhn lab
Depositing User: Matt Covey
Date: 20 July 2017
Date Deposited: 21 Jul 2017 21:03
Last Modified: 07 Jul 2021 18:58
PMCID: PMC7011612
Related URLs:
URI: https://repository.cshl.edu/id/eprint/35068

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