title: Endogenous 17β-estradiol is required for activity-dependent long-term potentiation in the striatum: interaction with the dopaminergic system.
abstract: 17β-estradiol (E2), a neurosteroid synthesized by P450-aromatase (ARO), modulates various brain functions. We characterized the role of the locally synthesized E2 on striatal long-term synaptic plasticity and explored possible interactions between E2 receptors (ERs) and dopamine (DA) receptors in the dorsal striatum of adult male rats. Inhibition of E2 synthesis or antagonism of ERs prevented the induction of long-term potentiation (LTP) in both medium spiny neurons (MSNs) and cholinergic interneurons (ChIs). Activation of a D1-like DA receptor/cAMP/PKA-dependent pathway restored LTP. In MSNs exogenous E2 reversed the effect of ARO inhibition. Also antagonism of M1 muscarinic receptors prevented the D1-like receptor-mediated restoration of LTP confirming a role for ChIs in controlling the E2-mediated LTP of MSNs. A novel striatal interaction, occurring between ERs and D1-like receptors in both MSNs and ChIs, might be critical to regulate basal ganglia physiology and to compensate synaptic alterations in Parkinson's disease.
authors.affiliation: Department of Experimental Medicine, Section of Physiology and Biochemistry, University of Perugia Perugia, Italy ; Fondazione Santa Lucia, IRCCS Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Tozzi
authors.affiliation: Clinica Neurologica, Dipartimento di Medicina, Università degli Studi di Perugia, Ospedale Santa Maria della Misericordia Perugia, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: de Iure
authors.affiliation: Clinica Neurologica, Dipartimento di Medicina, Università degli Studi di Perugia, Ospedale Santa Maria della Misericordia Perugia, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Tantucci
authors.affiliation: Clinica Neurologica, Dipartimento di Medicina, Università degli Studi di Perugia, Ospedale Santa Maria della Misericordia Perugia, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Durante
authors.affiliation: Clinica Neurologica, Dipartimento di Medicina, Università degli Studi di Perugia, Ospedale Santa Maria della Misericordia Perugia, Italy.
authors.forename: Ana
authors.initials: A
authors.lastname: Quiroga-Varela
authors.affiliation: Fondazione Santa Lucia, IRCCS Rome, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Giampà
authors.affiliation: Department of Experimental Medicine, Section of Physiology and Biochemistry, University of Perugia Perugia, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Di Mauro
authors.affiliation: Clinica Neurologica, Dipartimento di Medicina, Università degli Studi di Perugia, Ospedale Santa Maria della Misericordia Perugia, Italy.
authors.forename: Petra
authors.initials: P
authors.lastname: Mazzocchetti
authors.affiliation: Clinica Neurologica, Dipartimento di Medicina, Università degli Studi di Perugia, Ospedale Santa Maria della Misericordia Perugia, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Costa
authors.affiliation: Clinica Neurologica, Dipartimento di Medicina, Università degli Studi di Perugia, Ospedale Santa Maria della Misericordia Perugia, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Di Filippo
authors.affiliation: Department of Experimental Medicine, Section of Physiology and Biochemistry, University of Perugia Perugia, Italy.
authors.forename: Silvarosa
authors.initials: S
authors.lastname: Grassi
authors.affiliation: Department of Experimental Medicine, Section of Physiology and Biochemistry, University of Perugia Perugia, Italy.
authors.forename: Vito Enrico
authors.initials: VE
authors.lastname: Pettorossi
authors.affiliation: Fondazione Santa Lucia, IRCCS Rome, Italy ; Clinica Neurologica, Dipartimento di Medicina, Università degli Studi di Perugia, Ospedale Santa Maria della Misericordia Perugia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Calabresi
keywords: D1 receptor; P450-aromatase; cholinergic interneurons; estrogen receptors; long-term potentiation; medium spiny neurons; striatum; synaptic plasticity