Abstract
Anti-Müllerian hormone (AMH) is a paracrine factor generated peripherally by the gonads to regulate gonadal function in adult mammals. We recently reported that AMH and AMH-specific receptor Anti-Müllerian hormone receptor 2 (AMHR2) are expressed in the hippocampus, and exogenous AMH protein rapidly increased synaptic transmission and long-term synaptic plasticity at the CA3-CA1 synapses. Here we examined the cell-specific expression of AMHR2 and the cellular mechanism of rapid boosting effect of AMH on synaptic transmission in mouse hippocampus. Immunofluorescence staining showed that AMHR2 was specifically expressed in the soma and dendrites of hippocampal pyramidal neurons, but not glial cells. Electrophysiological recordings on acute hippocampal slices showed that AMH did not affect AMPAR-mediated or N-Methyl-D-aspartic acid receptor (NMDAR)-mediated excitatory postsynaptic currents at the CA3-CA1 synapses. The small-conductance Ca2+-activated K+ channel (SK2) and A-type K+ channel (Kv4.2) contribute to shaping excitatory postsynaptic potentials (EPSPs) at the CA3-CA1 synapses. Bath application of apamin to block SK2 did not alter AMH effect on increasing EPSPs, whereas blocking Kv4.2 channel with 4-aminopyridine, or chelating internal Ca2+ with BAPTA occluded the action of AMH on boosting EPSPs. Kv4.2 activity is regulated by p38 mitogen-activated kinase (MAPK). Blocking p38 MAPK with SB203580 occluded the effect of AMH on increasing EPSPs. These results show that Kv4.2 channel contributes to the rapid action of AMH on boosting synaptic transmission in a Ca2+- and p38 MAPK-dependent manner. Our findings provide functional evidence that AMH enhances synaptic transmission through Kv4.2 channel in the hippocampus, suggesting a possible role of Kv4.2 channel in AMH-regulated neuronal process underlying learning and memory.
Highlights
We further tested the hypothesis that anti-Müllerian hormone (AMH) binding to Anti-Müllerian hormone receptor 2 (AMHR2) activates downstream mitogen-activated protein kinase (MAPK) signaling pathways, which regulates Kv4.2 channel function and alters synaptic transmission
Bath application of 10 μM SB203580 by itself did not affect excitatory postsynaptic potentials (EPSPs) (91.6 ± 9.7, n = 5, p = 0.39) (Figures 7C,D). These results demonstrate that MAPK is required for the direct actions of AMH on boosting EPSPs, suggesting an AMHAMHR2-MAPK-Kv4.2 signaling pathway in regulating synaptic transmission in the hippocampus
We studied the cell-specific expression of AMHR2 and the mechanism by which AMH increases synaptic transmission in the hippocampus
Summary
Since its first discovery in 1947 by Alfred Jost, numerous studies have expanded the function of anti-Müllerian hormone (AMH) from its eponymous role in sex differentiation to neuroendocrine roles contributing to reproductive fitness and brain circuits (Cate et al, 1986; Munsterberg and Lovell-Badge, 1991; Lee et al, 1996; Lebeurrier et al, 2008; Wang et al, 2009, 2020; Cimino et al, 2016; Tata et al, 2018; Malone et al, 2019). Our findings show that AMH is locally generated in the brain, and rapidly increases synaptic strength and long-term synaptic plasticity (LTP) in the hippocampal CA3-CA1 synapses in mice (Wang et al, 2020). These results clearly demonstrate a role of AMH in regulating synaptic transmission in a postsynaptic manner, the underlying mechanism requires further investigation, such as a potential intracellular signaling pathway that delineates the AMH effect on boosting synaptic transmission
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.
