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Synaptic Dysfunction in Parkinson’s Disease

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Synaptic Plasticity

Part of the book series: Advances in Experimental Medicine and Biology ((volume 970))

Abstract

Activity-dependent modifications in synaptic efficacy, such as long-term depression (LTD) and long-term potentiation (LTP), represent key cellular substrates for adaptive motor control and procedural memory. The impairment of these two forms of synaptic plasticity in the nucleus striatum could account for the onset and the progression of motor and cognitive symptoms of Parkinson’s disease (PD), characterized by the massive degeneration of dopaminergic neurons. In fact, both LTD and LTP are peculiarly controlled and modulated by dopaminergic transmission coming from nigrostriatal terminals.

Changes in corticostriatal and nigrostriatal neuronal excitability may influence profoundly the threshold for the induction of synaptic plasticity, and changes in striatal synaptic transmission efficacy are supposed to play a role in the occurrence of PD symptoms. Understanding of these maladaptive forms of synaptic plasticity has mostly come from the analysis of experimental animal models of PD. A series of cellular and synaptic alterations occur in the striatum of experimental parkinsonism in response to the massive dopaminergic loss. In particular, dysfunctions in trafficking and subunit composition of glutamatergic NMDA receptors on striatal efferent neurons contribute to the clinical features of the experimental parkinsonism.

Interestingly, it has become increasingly evident that in striatal spiny neurons, the correct assembly of NMDA receptor complex at the postsynaptic site is a major player in early phases of PD, and it is sensitive to distinct degrees of DA denervation. The molecular defects at the basis of PD progression may be not confined just at the postsynaptic neuron: accumulating evidences have recently shown that the genes linked to PD play a critical role at the presynaptic site. DA release into the synaptic cleft relies on a proper presynaptic vesicular transport; impairment of SV trafficking, modification of DA flow, and altered presynaptic plasticity have been described in several PD animal models. Furthermore, an impaired DA turnover has been described in presymptomatic PD patients. Thus, given the pathological events occurring precociously at the synapses of PD patients, post- and presynaptic sites may represent an adequate target for early therapeutic intervention.

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Authors and Affiliations

  1. Laboratorio di Neurofisiologia, Fondazione Santa Lucia I.R.C.C.S., 00143, Rome, Italy

    Barbara Picconi & Paolo Calabresi

  2. CNR Institute of Neuroscience, Milan, Italy

    Giovanni Piccoli

  3. Clinica Neurologica, Facoltà di Medicina e Chirurgia, Università degli Studi di Perugia, Ospedale S. Maria della Misericordia, 06156, Perugia, Italy

    Paolo Calabresi

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  1. Barbara Picconi
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  2. Giovanni Piccoli
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Correspondence to Paolo Calabresi .

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  1. , PG Neuroplasticity, Leibniz Institute for Neurobiology, Brenneckestraße 6, Magdeburg, 39118, Germany

    Michael R. Kreutz

  2. , Institute of Neuroscience, CR6 CNR-IN Consiglio Nazionale delle Ric, Via Vanvitelli, 32, Milano, 20129, Italy

    Carlo Sala

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Picconi, B., Piccoli, G., Calabresi, P. (2012). Synaptic Dysfunction in Parkinson’s Disease. In: Kreutz, M., Sala, C. (eds) Synaptic Plasticity. Advances in Experimental Medicine and Biology, vol 970. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0932-8_24

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