Abstract
Neuroactive estrogenic and androgenic steroids influence synaptic transmission, finely modulating synaptic plasticity in several brain regions including the hippocampus. While estrogens facilitate long-term potentiation (LTP), androgens are involved in the induction of long-term depression (LTD) and depotentiation (DP) of synaptic transmission. To examine sex neurosteroid-dependent LTP and LTD in single cells, patch-clamp recordings from hippocampal CA1 pyramidal neurons of male rats and selective antagonists for estrogen receptors (ERs) and androgen (AR) receptors were used. LTP induced by high-frequency stimulation (HFS) depended on activation of ERs since it was prevented by the ER antagonist ICI 182,780 in most of the neurons. Application of the selective antagonists for ERα (MPP) or ERβ (PHTPP) caused a reduction of the LTP amplitude, while these antagonists in combination, prevented LTP completely. LTP was never affected by blocking AR with the specific antagonist flutamide. Conversely, LTD and DP, elicited by low-frequency stimulation (LFS), were impeded by flutamide, but not by ICI 182,780, in most neurons. In few cells, LTD was even reverted to LTP by flutamide. Moreover, the combined application of both ER and AR antagonists completely prevented both LTP and LTD/DP in the same neuron. The current study demonstrates that the activation of ERs is necessary for inducing LTP in hippocampal pyramidal neurons, whereas the activation of ARs is required for LTD and DP. Moreover, both estrogen- and androgen-dependent LTP and LTD can be expressed in the same pyramidal neurons, suggesting that the activation of sex neurosteroids signaling pathways is responsible for bidirectional synaptic plasticity.
Highlights
The finding that either the estrogen receptors (ERs) or AR blockade has no effect on the membrane electrical properties and on the synaptic response of CA1 pyramidal cells (PCs) seems to exclude an influence of estrogenic and androgenic signals in regulating the basal neuronal excitability and synaptic responsiveness
This study demonstrated that hippocampal neurons can express either long-term potentiation (LTP) and long-term depression (LTD)/DP of synaptic transmission, depending on the activation of ERs by E2 or ARs by DHT
Patch-clamp recordings of CA1 hippocampal pyramidal neurons revealed that ERs antagonism by ICI prevents LTP in the majority of the cells with no effect on LTD or DP
Summary
The sex steroids 17β-estradiol (E2), testosterone (T) and 5α-dihydrotestosterone (DHT) participate in the rapid modulation of long-term potentiation (LTP) and long-term depression (LTD) in different brain areas (McEwen, 2002; Isgor and Sengelaub, 2003; MacLusky et al, 2006; Hajszan et al, 2008; Grassi et al, 2011, 2013; Pettorossi et al, 2013; Scarduzio et al, 2013; Di Mauro et al, 2015, 2017; Tozzi et al, 2015). We tested the influence of ER and AR activation on LTP and LTD/DP, induced by high and low-frequency stimulation (LFS) protocols, respectively
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
