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J Neural Transm (Vienna). 2018 Aug;125(8):1263-1271. doi: 10.1007/s00702-018-1864-6. Epub 2018 Feb 28.

Synaptic plasticity and levodopa-induced dyskinesia: electrophysiological and structural abnormalities.

Author information

1
Laboratory of Neurophysiology, IRCCS Fondazione Santa Lucia c/o CERC, via del Fosso di Fiorano 64, 00143, Rome, Italy. b.picconi@hsantalucia.it.
2
Institute of Genetics and Biophysics (IGB), National Research Council, Naples, Italy.
3
Telethon Institute of Genetics and Medicine, Telethon Foundation, Pozzuoli, Italy.
4
Laboratory of Neurophysiology, IRCCS Fondazione Santa Lucia c/o CERC, via del Fosso di Fiorano 64, 00143, Rome, Italy.
5
Clinica Neurologica, Università degli studi di Perugia, Ospedale Santa Maria della Misericordia, S. Andrea delle Fratte, 06156, Perugia, Italy.

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive degeneration of dopaminergic neurons located in the midbrain. The gold-standard therapy for PD is the restoration of dopamine (DA) levels through the chronic administration of the DA precursor levodopa (L-DOPA). Although levodopa therapy is the main therapeutic approach for PD, its use is limited by the development of very disabling dyskinetic movements, mainly due to the fluctuation of DA cerebral content. Experimental animal models of PD identified in DA D1/ERK-signaling pathway aberrant activation, occurring in striatal projection neurons, coupled with structural spines abnormalities, the molecular and neuronal basis of L-DOPA-induced dyskinesia (LIDs) occurrence. Different electrophysiological approaches allowed the identification of  the alteration of homeostatic structural and synaptic changes, the neuronal bases of LIDs either in vivo in parkinsonian patients or in vitro in experimental animals. Here, we report the most recent studies showing electrophysiological and morphological evidence of aberrant synaptic plasticity in parkinsonian patients during LIDs in different basal ganglia nuclei and also in cortical transmission, accounting for the complexity of the synaptic changes during dyskinesias. All together, these studies suggest that LIDs are associated with a loss of homeostatic synaptic mechanisms.

KEYWORDS:

Depotentiation; LIDs; Parkinson’s disease; Spine plasticity; Synaptic plasticity

PMID:
29492662
DOI:
10.1007/s00702-018-1864-6

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