Dopamine-dependent long-term depression is expressed in striatal spiny neurons of both direct and indirect pathways: implications for Parkinson's disease

Vincenza Bagetta; Barbara Picconi; Silvia Marinucci; Carmelo Sgobio; Valentina Pendolino; Veronica Ghiglieri; Francesca R Fusco; Carmen Giampà; Paolo Calabresi

doi:10.1523/JNEUROSCI.2236-11.2011

Dopamine-dependent long-term depression is expressed in striatal spiny neurons of both direct and indirect pathways: implications for Parkinson's disease

J Neurosci. 2011 Aug 31;31(35):12513-22. doi: 10.1523/JNEUROSCI.2236-11.2011.

Authors

Vincenza Bagetta¹, Barbara Picconi, Silvia Marinucci, Carmelo Sgobio, Valentina Pendolino, Veronica Ghiglieri, Francesca R Fusco, Carmen Giampà, Paolo Calabresi

Affiliation

¹ Fondazione Santa Lucia, Instituto di Ricovero e Cura a Carattere Scientifico, 00143 Rome, Italy.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Analysis of Variance
Animals
Avoidance Learning / drug effects
Avoidance Learning / physiology
Biophysical Phenomena
Corpus Striatum / pathology*
Disease Models, Animal
Dopamine / metabolism*
Electric Stimulation
Excitatory Postsynaptic Potentials / drug effects
Excitatory Postsynaptic Potentials / genetics
Exploratory Behavior / drug effects
Exploratory Behavior / physiology
Green Fluorescent Proteins / genetics
Long-Term Synaptic Depression / drug effects
Long-Term Synaptic Depression / genetics
Long-Term Synaptic Depression / physiology*
Lysine / analogs & derivatives
Lysine / metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Motor Activity / genetics
Neurons / drug effects
Neurons / physiology*
Oxidopamine / toxicity
Parkinson Disease / etiology
Parkinson Disease / pathology*
Parkinson Disease / physiopathology
Rats
Rats, Wistar
Receptor, Adenosine A2A / metabolism
Receptors, Dopamine D1 / deficiency
Receptors, Dopamine D2 / deficiency
Substance P / metabolism

Substances

Receptor, Adenosine A2A
Receptors, Dopamine D1
Receptors, Dopamine D2
enhanced green fluorescent protein
Green Fluorescent Proteins
Substance P
Oxidopamine
biocytin
Lysine
Dopamine