title: Synaptic long-term potentiation and depression in the rat medial vestibular nuclei depend on neural activation of estrogenic and androgenic signals.
abstract: Estrogenic and androgenic steroids can be synthesised in the brain and rapidly modulate synaptic transmission and plasticity through direct interaction with membrane receptors for estrogens (ERs) and androgens (ARs). We used whole cell patch clamp recordings in brainstem slices of male rats to explore the influence of ER and AR activation and local synthesis of 17β-estradiol (E2) and 5α-dihydrotestosterone (DHT) on the long-term synaptic changes induced in the neurons of the medial vestibular nucleus (MVN). Long-term depression (LTD) and long-term potentiation (LTP) caused by different patterns of high frequency stimulation (HFS) of the primary vestibular afferents were assayed under the blockade of ARs and ERs or in the presence of inhibitors for enzymes synthesizing DHT (5α-reductase) and E2 (P450-aromatase) from testosterone (T). We found that LTD is mediated by interaction of locally produced androgens with ARs and LTP by interaction of locally synthesized E2 with ERs. In fact, the AR block with flutamide prevented LTD while did not affect LTP, and the blockade of ERs with ICI 182,780 abolished LTP without influencing LTD. Moreover, the block of P450-aromatase with letrozole not only prevented the LTP induction, but inverted LTP into LTD. This LTD is likely due to the local activation of androgens, since it was abolished under blockade of ARs. Conversely, LTD was still induced in the presence of finasteride the inhibitor of 5α-reductase demonstrating that T is able to activate ARs and induce LTD even when DHT is not synthesized. This study demonstrates a key and opposite role of sex neurosteroids in the long-term synaptic changes of the MVN with a specific role of T-DHT for LTD and of E2 for LTP. Moreover, it suggests that different stimulation patterns can lead to LTD or LTP by specifically activating the enzymes involved in the synthesis of androgenic or estrogenic neurosteroids.
authors.affiliation: Dipartimento di Medicina Interna, Sezione di Fisiologia Umana, Facoltà di Medicina e Chirurgia, Università di Perugia, Perugia, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Scarduzio
authors.forename: Roberto
authors.initials: R
authors.lastname: Panichi
authors.forename: Vito Enrico
authors.initials: VE
authors.lastname: Pettorossi
authors.forename: Silvarosa
authors.initials: S
authors.lastname: Grassi
mesh_terms: D000728:Androgens / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D012739:Gonadal Steroid Hormones / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014726:Vestibular Nuclei / Q000187:drug effects / Q000502:physiology*
chemical_list: D000728:Androgens; D004967:Estrogens; D012739:Gonadal Steroid Hormones