Long-term potentiation in the rat medial vestibular nuclei depends on locally synthesized 17beta-estradiol.
In male rat brainstem slices, we investigated the involvement of locally synthesized 17beta-estradiol (E(2)) in the induction in the medial vestibular nucleus (MVN) of long-term potentiation (LTP) by high-frequency stimulation (HFS) of the primary vestibular afferents. We demonstrated that the blockade of aromatase by letrozole or of E(2) receptors (ERalpha and ERbeta) by ICI 182,780 prevented the HFS-induced LTP of the N1 wave of the evoked field potential (FP) without affecting baseline responses. Only prolonged afferent activation could induce low LTP. In contrast, HFS applied under a combined blockade of GABA(A) receptors and aromatase or ERs was still able to induce LTP, but it was significantly lower and slower. These findings demonstrate that E(2) does not have a tonic influence on the activity of the MVN neurons and provide the first evidence of the crucial role played by local synthesis of E(2) in inducing LTP. We suggest that the synthesis of E(2) occurs after aromatase activation during HFS and facilitates the development of vestibular synaptic plasticity by influencing glutamate and GABA transmission.
Grassi
Silvarosa
S
Department of Internal Medicine, Section of Human Physiology, University of Perugia, I-06126 Perugia, Italy. sgrassi@unipg.it
Frondaroli
Adele
A
Dieni
Cristina
C
Scarduzio
Mariangela
M
Pettorossi
Vito E
VE
D000818:Animals; D000831:Animals, Newborn; D047072:Aromatase Inhibitors / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D001703:Biophysics; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D000077267:Fulvestrant; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D000077289:Letrozole; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014230:Triazoles / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D014726:Vestibular Nuclei / Q000378:metabolism* / Q000502:physiology*
D047072:Aromatase Inhibitors; D004965:Estrogen Antagonists; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D009570:Nitriles; D011810:Quinoxalines; D014230:Triazoles; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D000077267:Fulvestrant; D004958:Estradiol; C056639:2-amino-5-phosphopentanoic acid; D000077289:Letrozole; D014633:Valine; D001640:Bicuculline