title: Effects of 17beta-estradiol on glutamate synaptic transmission and neuronal excitability in the rat medial vestibular nuclei.
abstract: We investigated the effects of the neurosteroid 17beta-estradiol (E(2)) on the evoked and spontaneous activity of rat medial vestibular nucleus (MVN) neurons in brainstem slices. E(2) enhances the synaptic response to vestibular nerve stimulation in type B neurons and depresses the spontaneous discharge in both type A and B neurons. The amplitude of the field potential, as well as the excitatory post-synaptic potential (EPSP) and current (EPSC), in type B neurons, are enhanced by E(2). Both effects are long-term phenomena since they outlast the drug washout. The enhancement of synaptic response is mainly due to facilitation of glutamate release mediated by pre-synaptic N-methyl-D-aspartate receptors (NMDARs), since the reduction of paired pulse ratio (PPR) and the increase of miniature EPSC frequency after E(2) are abolished under D-(-)-2-amino-5-phosphonopentanoic acid (AP-5). E(2) also facilitates post-synaptic NMDARs, but it does not affect directly alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and group I-metabotropic glutamate receptors (mGluRs-I). In contrast, the depression of the spontaneous discharge of type A and type B neurons appears to depend on E(2) modulation of intrinsic ion conductances, as the effect remains after blockade of glutamate, GABA and glycine receptors (GlyRs). The net effect of E(2) is to enhance the signal-to-noise ratio of the synaptic response in type B neurons, relative to resting activity of all MVN neurons. These findings provide evidence for a novel potential mechanism to modulate the responsiveness of vestibular neurons to afferent inputs, and so regulate vestibular function in vivo.
authors: Department of Internal Medicine, Section of Human Physiology, University of Perugia, Perugia, Italy. sgrassi@unipg.it
authors: S
authors: S
authors: Grassi
authors: A
authors: A
authors: Frondaroli
authors: M
authors: M
authors: Scarduzio
authors: M B
authors: MB
authors: Dutia
authors: C
authors: C
authors: Dieni
authors: V E
authors: VE
authors: Pettorossi
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism; D018079:Receptors, GABA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D018009:Receptors, Glycine / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D014725:Vestibular Nerve / Q000502:physiology; D014726:Vestibular Nuclei / Q000187:drug effects* / Q000502:physiology
chemical_list: D004967:Estrogens; D018091:Receptors, AMPA; D018079:Receptors, GABA; D017470:Receptors, Glutamate; D018009:Receptors, Glycine; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C104077:metabotropic glutamate receptor type 1; D018698:Glutamic Acid; D004958:Estradiol