RT Journal Article
SR Electronic
T1 Distal Dendritic Enrichment of HCN1 Channels in Hippocampal CA1 Is Promoted by Estrogen, but Does Not Require Reelin
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0258-18.2018
DO 10.1523/ENEURO.0258-18.2018
VO 5
IS 5
A1 Maurice Meseke
A1 Florian Neumüller
A1 Bianka Brunne
A1 Xiaoyu Li
A1 Max Anstötz
A1 Theresa Pohlkamp
A1 Meike M. Rogalla
A1 Joachim Herz
A1 Gabriele M. Rune
A1 Roland A. Bender
YR 2018
UL http://www.eneuro.org/content/5/5/ENEURO.0258-18.2018.abstract
AB HCN1 compartmentalization in CA1 pyramidal cells, essential for hippocampal information processing, is believed to be controlled by the extracellular matrix protein Reelin. Expression of Reelin, in turn, is stimulated by 17β-estradiol (E2). In this study, we therefore tested whether E2 regulates the compartmentalization of HCN1 in CA1 via Reelin. In organotypic entorhino-hippocampal cultures, we found that E2 promotes HCN1 distal dendritic enrichment via the G protein–coupled estrogen receptor GPER1, but apparently independent of Reelin, because GST-RAP, known to reduce Reelin signaling, did not prevent E2-induced HCN1 enrichment in distal CA1. We therefore re-examined the role of Reelin for the regulation of HCN1 compartmentalization and could not detect effects of reduced Reelin signaling on HCN1 distribution in CA1, either in the (developmental) slice culture model or in tamoxifen-inducible conditional reelin knockout mice during adulthood. We conclude that for HCN1 channel compartmentalization in CA1 pyramidal cells, Reelin is not as essential as previously proposed, and E2 effects on HCN1 distribution in CA1 are mediated by mechanisms that do not involve Reelin. Because HCN1 localization was not altered at different phases of the estrous cycle, gonadally derived estradiol is unlikely to regulate HCN1 channel compartmentalization, while the pattern of immunoreactivity of aromatase, the final enzyme of estradiol synthesis, argues for a role of local hippocampal E2 synthesis.