title: Dopamine-dependent long-term depression is expressed in striatal spiny neurons of both direct and indirect pathways: implications for Parkinson's disease.
abstract: Striatal medium spiny neurons (MSNs) are divided into two subpopulations exerting distinct effects on motor behavior. Transgenic mice carrying bacterial artificial chromosome (BAC) able to confer cell type-specific expression of enhanced green fluorescent protein (eGFP) for dopamine (DA) receptors have been developed to characterize differences between these subpopulations. Analysis of these mice, in contrast with original pioneering studies, showed that striatal long-term depression (LTD) was expressed in indirect but not in the direct pathway MSNs. To address this mismatch, we applied a new approach using combined BAC technology and receptor immunohistochemistry. We demonstrate that, in physiological conditions, DA-dependent LTD is expressed in both pathways showing that the lack of synaptic plasticity found in D(1) eGFP mice is associated to behavioral deficits. Our findings suggest caution in the use of this tool and indicate that the "striatal segregation" hypothesis might not explain all synaptic dysfunctions in Parkinson's disease.
authors: Fondazione Santa Lucia, Instituto di Ricovero e Cura a Carattere Scientifico, 00143 Rome, Italy.
authors: Vincenza
authors: V
authors: Bagetta
authors: Barbara
authors: B
authors: Picconi
authors: Silvia
authors: S
authors: Marinucci
authors: Carmelo
authors: C
authors: Sgobio
authors: Valentina
authors: V
authors: Pendolino
authors: Veronica
authors: V
authors: Ghiglieri
authors: Francesca R
authors: FR
authors: Fusco
authors: Carmen
authors: C
authors: Giampà
authors: Paolo
authors: P
authors: Calabresi
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D055592:Biophysical Phenomena; D003342:Corpus Striatum / Q000473:pathology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000172:deficiency; D017448:Receptors, Dopamine D2 / Q000172:deficiency; D013373:Substance P / Q000378:metabolism
chemical_list: D043705:Receptor, Adenosine A2A; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D013373:Substance P; D016627:Oxidopamine; C013411:biocytin; D008239:Lysine; D004298:Dopamine