Dopamine-Dependent Long-Term Depression Is Expressed in Striatal Spiny Neurons of Both Direct and Indirect Pathways: Implications for Parkinson's Disease

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 D1 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.

[1]  R. Palmiter,et al.  Requirement of dopamine signaling in the amygdala and striatum for learning and maintenance of a conditioned avoidance response. , 2011, Learning & memory.

[2]  P. Calabresi,et al.  The Distinct Role of Medium Spiny Neurons and Cholinergic Interneurons in the D2/A2A Receptor Interaction in the Striatum: Implications for Parkinson's Disease , 2011, The Journal of Neuroscience.

[3]  P. Calabresi,et al.  Inhibition of phosphodiesterases rescues striatal long-term depression and reduces levodopa-induced dyskinesia. , 2011, Brain : a journal of neurology.

[4]  D. Sibley,et al.  Dopamine D2 Receptor Overexpression Alters Behavior and Physiology in Drd2-EGFP Mice , 2011, Journal of Neuroscience.

[5]  P. Calabresi,et al.  Levodopa-induced dyskinesias in patients with Parkinson's disease: filling the bench-to-bedside gap , 2010, The Lancet Neurology.

[6]  P. Greengard,et al.  Distinct Levels of Dopamine Denervation Differentially Alter Striatal Synaptic Plasticity and NMDA Receptor Subunit Composition , 2010, The Journal of Neuroscience.

[7]  David M. Lovinger,et al.  Neurotransmitter roles in synaptic modulation, plasticity and learning in the dorsal striatum , 2010, Neuropharmacology.

[8]  Paolo Calabresi,et al.  Synaptic dysfunction in Parkinson's disease. , 2012, Advances in experimental medicine and biology.

[9]  Yvette E. Fisher,et al.  Dopamine modulation of excitatory currents in the striatum is dictated by the expression of D1 or D2 receptors and modified by endocannabinoids , 2010, The European journal of neuroscience.

[10]  P. Calabresi,et al.  Short-term and long-term plasticity at corticostriatal synapses: Implications for learning and memory , 2009, Behavioural Brain Research.

[11]  Jean-Michel Deniau,et al.  Striatal Medium-Sized Spiny Neurons: Identification by Nuclear Staining and Study of Neuronal Subpopulations in BAC Transgenic Mice , 2009, PloS one.

[12]  Paul Greengard,et al.  Histone H3 Phosphorylation is Under the Opposite Tonic Control of Dopamine D2 and Adenosine A2A Receptors in Striatopallidal Neurons , 2009, Neuropsychopharmacology.

[13]  P. Greengard,et al.  Dichotomous Dopaminergic Control of Striatal Synaptic Plasticity , 2008, Science.

[14]  J. Girault,et al.  Opposing Patterns of Signaling Activation in Dopamine D1 and D2 Receptor-Expressing Striatal Neurons in Response to Cocaine and Haloperidol , 2008, The Journal of Neuroscience.

[15]  P. Calabresi,et al.  l-DOPA dosage is critically involved in dyskinesia via loss of synaptic depotentiation , 2008, Neurobiology of Disease.

[16]  Max Kleiman-Weiner,et al.  Differential electrophysiological properties of dopamine D1 and D2 receptor‐containing striatal medium‐sized spiny neurons , 2008, The European journal of neuroscience.

[17]  Kristen K. Ade,et al.  Differential Tonic GABA Conductances in Striatal Medium Spiny Neurons , 2008, The Journal of Neuroscience.

[18]  O. Güntürkün,et al.  Non‐motor behavioural impairments in parkin‐deficient mice , 2007, The European journal of neuroscience.

[19]  Paolo Calabresi,et al.  Dopamine-mediated regulation of corticostriatal synaptic plasticity , 2007, Trends in Neurosciences.

[20]  Robert C. Malenka,et al.  Endocannabinoid-mediated rescue of striatal LTD and motor deficits in Parkinson's disease models , 2007, Nature.

[21]  A. Reiner,et al.  Differential perikaryal localization in rats of D1 and D2 dopamine receptors on striatal projection neuron types identified by retrograde labeling , 2006, Journal of Chemical Neuroanatomy.

[22]  P. Calabresi,et al.  A convergent model for cognitive dysfunctions in Parkinson's disease: the critical dopamine–acetylcholine synaptic balance , 2006, The Lancet Neurology.

[23]  Henry H. Yin,et al.  Dopaminergic Control of Corticostriatal Long-Term Synaptic Depression in Medium Spiny Neurons Is Mediated by Cholinergic Interneurons , 2006, Neuron.

[24]  A. Sampson,et al.  Selective elimination of glutamatergic synapses on striatopallidal neurons in Parkinson disease models , 2006, Nature Neuroscience.

[25]  R. Cunha,et al.  Different synaptic and subsynaptic localization of adenosine A2A receptors in the hippocampus and striatum of the rat , 2005, Neuroscience.

[26]  A. Graybiel.  The basal ganglia: learning new tricks and loving it , 2005, Current Opinion in Neurobiology.

[27]  P. Calabresi,et al.  Nigrostriatal Dopaminergic Deficits and Hypokinesia Caused by Inactivation of the Familial Parkinsonism-Linked Gene DJ-1 , 2005, Neuron.

[28]  H. Lindgren,et al.  A model of l-DOPA-induced dyskinesia in 6-hydroxydopamine lesioned mice: relation to motor and cellular parameters of nigrostriatal function , 2004, Neurobiology of Disease.

[29]  Amy Lee,et al.  Anatomy of adenosine A2A receptors in brain , 2003, Neurology.

[30]  Shiaoching Gong,et al.  A gene expression atlas of the central nervous system based on bacterial artificial chromosomes , 2003, Nature.

[31]  Paul Greengard,et al.  Loss of bidirectional striatal synaptic plasticity in L-DOPA–induced dyskinesia , 2003, Nature Neuroscience.

[32]  Jørn Müller.  Impact of Cancer Therapy on the Reproductive Axis , 2003, Hormone Research in Paediatrics.

[33]  N. Canteras,et al.  The Lesion of the Rat Substantia Nigra pars compacta Dopaminergic Neurons as a Model for Parkinson's Disease Memory Disabilities , 2002, Cellular and Molecular Neurobiology.

[34]  D. Lovinger,et al.  Postsynaptic endocannabinoid release is critical to long-term depression in the striatum , 2002, Nature Neuroscience.

[35]  R. J. McDonald,et al.  Multiple Parallel Memory Systems in the Brain of the Rat , 2002, Neurobiology of Learning and Memory.

[36]  E. Kandel.  The Molecular Biology of Memory Storage: A Dialogue Between Genes and Synapses , 2001, Science.

[37]  K. Tang,et al.  Dopamine-dependent synaptic plasticity in striatum during in vivo development. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[38]  P. Svenningsson,et al.  Distribution, biochemistry and function of striatal adenosine A2A receptors , 1999, Progress in Neurobiology.

[39]  P. Calabresi,et al.  Glutamate-Triggered Events Inducing Corticostriatal Long-Term Depression , 1999, The Journal of Neuroscience.

[40]  R. J. McDonald,et al.  Effects of medial and lateral caudate-putamen lesions on place- and cue-guided behaviors in the water maze: relation to thigmotaxis , 1999, Behavioural Brain Research.

[41]  J. Costentin,et al.  Thigmotaxis as an index of anxiety in mice. Influence of dopaminergic transmissions , 1994, Behavioural Brain Research.

[42]  D. Lovinger,et al.  Short- and long-term synaptic depression in rat neostriatum. , 1993, Journal of neurophysiology.

[43]  P. Calabresi,et al.  Long-term synaptic depression in the striatum: physiological and pharmacological characterization , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[44]  P. Calabresi,et al.  Coactivation of D1 and D2 dopamine receptors is required for long-term synaptic depression in the striatum , 1992, Neuroscience Letters.

[45]  C. Gerfen,et al.  D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. , 1990, Science.

[46]  Charles Watson,et al.  Bregma, lambda and the interaural midpoint in stereotaxic surgery with rats of different sex, strain and weight , 1985, Journal of Neuroscience Methods.

[47]  R. M. Beckstead,et al.  Immunohistochemical demonstration of differential substance P‐, met‐ enkephalin‐, and glutamic‐acid‐decarboxylase‐containing cell body and axon distributions in the corpus striatum of the cat , 1985, The Journal of comparative neurology.

[48]  G. Koob,et al.  Neuroleptic-like distruption of the conditioned avoidance response requires destruction of both the mesolimbic and nigrostriatal dopamine systems , 1984, Brain Research.

[49]  S. T. Mason,et al.  THE EFFECTS OF DORSAL BUNDLE INJECTIONS OF 6‐HYDROXYDOPAMINE ON AVOIDANCE RESPONDING IN RATS , 1978, British journal of pharmacology.

[50]  Paolo Calabresi,et al.  Neuronal networks and synaptic plasticity in Parkinson's disease: beyond motor deficits. , 2007, Parkinsonism & related disorders.

[51]  C. Gerfen.  The neostriatal mosaic: multiple levels of compartmental organization in the basal ganglia. , 1992, Annual review of neuroscience.