Motor learning and metaplasticity in striatal neurons: relevance for Parkinson's disease

Nadia Giordano, Attilio Iemolo, Maria Mancini, Fabrizio Cacace, Maria De Risi, Emanuele Claudio Latagliata, Veronica Ghiglieri, Gian Carlo Bellenchi, Stefano Puglisi-Allegra, Paolo Calabresi, Barbara Picconi, Elvira De Leonibus

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Nigro-striatal dopamine transmission is central to a wide range of neuronal functions, including skill learning, which is disrupted in several pathologies such as Parkinson's disease. The synaptic plasticity mechanisms, by which initial motor learning is stored for long time periods in striatal neurons, to then be gradually optimized upon subsequent training, remain unexplored. Addressing this issue is crucial to identify the synaptic and molecular mechanisms involved in striatal-dependent learning impairment in Parkinson's disease. In this study, we took advantage of interindividual differences between outbred rodents in reaching plateau performance in the rotarod incremental motor learning protocol, to study striatal synaptic plasticity ex vivo. We then assessed how this process is modulated by dopamine receptors and the dopamine active transporter, and whether it is impaired by overexpression of human α-synuclein in the mesencephalon; the latter is a progressive animal model of Parkinson's disease. We found that the initial acquisition of motor learning induced a dopamine active transporter and D1 receptors mediated long-term potentiation, under a protocol of long-term depression in striatal medium spiny neurons. This effect disappeared in animals reaching performance plateau. Overexpression of human α-synuclein reduced striatal dopamine active transporter levels, impaired motor learning, and prevented the learning-induced long-term potentiation, before the appearance of dopamine neuronal loss. Our findings provide evidence of a reorganization of cellular plasticity within the dorsolateral striatum that is mediated by dopamine receptors and dopamine active transporter during the acquisition of a skill. This newly identified mechanism of cellular memory is a form of metaplasticity that is disrupted in the early stage of synucleinopathies, such as Parkinson's disease, and that might be relevant for other striatal pathologies, such as drug abuse.

Original languageEnglish
Pages (from-to)505-520
Number of pages16
JournalBrain : a journal of neurology
Volume141
Issue number2
DOIs
Publication statusE-pub ahead of print - Dec 21 2017

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Corpus Striatum
Parkinson Disease
Learning
Dopamine Plasma Membrane Transport Proteins
Neurons
Synucleins
Neuronal Plasticity
Long-Term Potentiation
Dopamine Receptors
Dopamine
Pathology
Mesencephalon
Substance-Related Disorders
Rodentia
Animal Models
Depression

Keywords

  • Journal Article

Cite this

Giordano, N., Iemolo, A., Mancini, M., Cacace, F., De Risi, M., Latagliata, E. C., ... De Leonibus, E. (2017). Motor learning and metaplasticity in striatal neurons: relevance for Parkinson's disease. Brain : a journal of neurology, 141(2), 505-520. https://doi.org/10.1093/brain/awx351

Motor learning and metaplasticity in striatal neurons : relevance for Parkinson's disease. / Giordano, Nadia; Iemolo, Attilio; Mancini, Maria; Cacace, Fabrizio; De Risi, Maria; Latagliata, Emanuele Claudio; Ghiglieri, Veronica; Bellenchi, Gian Carlo; Puglisi-Allegra, Stefano; Calabresi, Paolo; Picconi, Barbara; De Leonibus, Elvira.

In: Brain : a journal of neurology, Vol. 141, No. 2, 21.12.2017, p. 505-520.

Research output: Contribution to journalArticle

Giordano, N, Iemolo, A, Mancini, M, Cacace, F, De Risi, M, Latagliata, EC, Ghiglieri, V, Bellenchi, GC, Puglisi-Allegra, S, Calabresi, P, Picconi, B & De Leonibus, E 2017, 'Motor learning and metaplasticity in striatal neurons: relevance for Parkinson's disease', Brain : a journal of neurology, vol. 141, no. 2, pp. 505-520. https://doi.org/10.1093/brain/awx351
Giordano N, Iemolo A, Mancini M, Cacace F, De Risi M, Latagliata EC et al. Motor learning and metaplasticity in striatal neurons: relevance for Parkinson's disease. Brain : a journal of neurology. 2017 Dec 21;141(2):505-520. https://doi.org/10.1093/brain/awx351
Giordano, Nadia ; Iemolo, Attilio ; Mancini, Maria ; Cacace, Fabrizio ; De Risi, Maria ; Latagliata, Emanuele Claudio ; Ghiglieri, Veronica ; Bellenchi, Gian Carlo ; Puglisi-Allegra, Stefano ; Calabresi, Paolo ; Picconi, Barbara ; De Leonibus, Elvira. / Motor learning and metaplasticity in striatal neurons : relevance for Parkinson's disease. In: Brain : a journal of neurology. 2017 ; Vol. 141, No. 2. pp. 505-520.
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AU - De Leonibus, Elvira

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N2 - Nigro-striatal dopamine transmission is central to a wide range of neuronal functions, including skill learning, which is disrupted in several pathologies such as Parkinson's disease. The synaptic plasticity mechanisms, by which initial motor learning is stored for long time periods in striatal neurons, to then be gradually optimized upon subsequent training, remain unexplored. Addressing this issue is crucial to identify the synaptic and molecular mechanisms involved in striatal-dependent learning impairment in Parkinson's disease. In this study, we took advantage of interindividual differences between outbred rodents in reaching plateau performance in the rotarod incremental motor learning protocol, to study striatal synaptic plasticity ex vivo. We then assessed how this process is modulated by dopamine receptors and the dopamine active transporter, and whether it is impaired by overexpression of human α-synuclein in the mesencephalon; the latter is a progressive animal model of Parkinson's disease. We found that the initial acquisition of motor learning induced a dopamine active transporter and D1 receptors mediated long-term potentiation, under a protocol of long-term depression in striatal medium spiny neurons. This effect disappeared in animals reaching performance plateau. Overexpression of human α-synuclein reduced striatal dopamine active transporter levels, impaired motor learning, and prevented the learning-induced long-term potentiation, before the appearance of dopamine neuronal loss. Our findings provide evidence of a reorganization of cellular plasticity within the dorsolateral striatum that is mediated by dopamine receptors and dopamine active transporter during the acquisition of a skill. This newly identified mechanism of cellular memory is a form of metaplasticity that is disrupted in the early stage of synucleinopathies, such as Parkinson's disease, and that might be relevant for other striatal pathologies, such as drug abuse.

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