title: Coordinated Regulation of Synaptic Plasticity at Striatopallidal and Striatonigral Neurons Orchestrates Motor Control.
abstract: The basal ganglia play a critical role in shaping motor behavior. For this function, the activity of medium spiny neurons (MSNs) of the striatonigral and striatopallidal pathways must be integrated. It remains unclear whether the activity of the two pathways is primarily coordinated by synaptic plasticity mechanisms. Using a model of Parkinson's disease, we determined the circuit and behavioral effects of concurrently regulating cell-type-specific forms of corticostriatal long-term synaptic depression (LTD) by inhibiting small-conductance Ca(2+)-activated K(+) channels (SKs) of the dorsolateral striatum. At striatopallidal synapses, SK channel inhibition rescued the disease-linked deficits in endocannabinoid (eCB)-dependent LTD. At striatonigral cells, inhibition of these channels counteracted a form of adenosine-mediated LTD by activating the ERK cascade. Interfering with eCB-, adenosine-, and ERK signaling in vivo alleviated motor abnormalities, which supports that synaptic modulation of striatal pathways affects behavior. Thus, our results establish a central role of coordinated synaptic plasticity at MSN subpopulations in motor control.
authors.affiliation: Neuroscience and Brain Technologies Department, Istituto Italiano di Tecnologia, 16163 Genova, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Trusel
authors.affiliation: Neuroscience and Brain Technologies Department, Istituto Italiano di Tecnologia, 16163 Genova, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Cavaccini
authors.affiliation: Neuroscience and Brain Technologies Department, Istituto Italiano di Tecnologia, 16163 Genova, Italy; Life Science Department, University of Milan, 20133 Milano, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Gritti
authors.affiliation: Neuroscience and Brain Technologies Department, Istituto Italiano di Tecnologia, 16163 Genova, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Greco
authors.affiliation: Neuroscience and Brain Technologies Department, Istituto Italiano di Tecnologia, 16163 Genova, Italy.
authors.forename: Pierre-Philippe
authors.initials: PP
authors.lastname: Saintot
authors.affiliation: Neuroscience and Brain Technologies Department, Istituto Italiano di Tecnologia, 16163 Genova, Italy.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Nazzaro
authors.affiliation: IRCCS, Mario Negri Institute for Pharmacological Research, 20156 Milano, Italy; Neuroscience and Mental Health Research Institute, Division of Neuroscience, School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK.
authors.forename: Milica
authors.initials: M
authors.lastname: Cerovic
authors.affiliation: Neuroscience and Mental Health Research Institute, Division of Neuroscience, School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK; Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute and University, 20132 Milano, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Morella
authors.affiliation: IRCCS, Mario Negri Institute for Pharmacological Research, 20156 Milano, Italy; Neuroscience and Mental Health Research Institute, Division of Neuroscience, School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Brambilla
authors.affiliation: Neuroscience and Brain Technologies Department, Istituto Italiano di Tecnologia, 16163 Genova, Italy. Electronic address: raffaella.tonini@iit.it.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Tonini
mesh_terms: D000241:Adenosine / Q000502:physiology; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000473:pathology; D003342:Corpus Striatum / Q000473:pathology*; D004298:Dopamine / Q000502:physiology; D059290:Dopaminergic Neurons / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials; D036881:Long-Term Synaptic Depression; D020935:MAP Kinase Signaling System; D051379:Mice; D009043:Motor Activity; D009473:Neuronal Plasticity; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000473:pathology; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D013378:Substantia Nigra / Q000473:pathology*
chemical_list: D043682:Receptor, Adenosine A1; D051640:Small-Conductance Calcium-Activated Potassium Channels; D000241:Adenosine; D004298:Dopamine