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Non‐motor Function of the Midbrain Dopaminergic Neurons

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Birth, Life and Death of Dopaminergic Neurons in the Substantia Nigra

Part of the book series: Journal of Neural Transmission. Supplementa ((NEURALTRANS,volume 73))

Abstract

The roles of the nigrostriatal pathway are far beyond the simple control of motor functions. The tonic release of dopamine in the dorsal and ventral striatum controls the choice of proper actions toward a given environmental situation. In the striatum, a specific action is triggered by a specific stimulus associated with it. When the subject faces a novel and salient stimulus, the phasic release of dopamine allows synaptic plasticity in the cortico-striatal synapses. Neurons of different regions of cortical areas make synapses that converge to the same medium spine neurons of the striatum. The convergent associations form functional units encoding body parts, objects, locations, and symbolic representations of the subject’s world. Such units emerge in the striatum in a repetitive manner, like a mosaic of broken mirrors. The phasic release of dopamine allows the association of units to encode an action of the subject directed to an object or location with the outcome of this action. Reinforced stimulus-action-outcome associations will affect future decision making when the same stimulus (object, location, idea) is presented to the subject in the future. In the absence of a minimal amount of striatal dopamine, no action is initiated as seen in Parkinson’s disease subjects. The abnormal and improper association of these units leads to the initiation of unpurposeful and sometimes repetitive actions, as those observed in dyskinetic patients. The association of an excessive reinforcement of some actions, like drug consumption, leads to drug addiction. Improper associations of ideas and unpleasant outcomes may be related to traumatic and depressive symptoms common in many diseases, including Parkinson’s disease. The same can be said about the learning and memory impairments observed in demented and nondemented Parkinson’s disease patients.

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Abbreviations

CREB:

Cyclic-AMPc response-element-binding protein

CRF:

Corticotrophin-releasing factor

DSM IV:

Diagnostic and statistical manual of mental disorders

GABA:

Gamma amino butyric acid

GPi:

Globus pallidus

HD:

Huntington’s disease

LTP:

Long-term potentiation

NAc:

Nucleus accumbens

PD:

Parkinson’s disease

PET:

Positron emission tomography

SNc:

Substantia nigra pars compacta

SNr:

Substantia nigra pars reticulata

TH:

Tyrosine hydroxylase

THC:

Tetrahydrocannabinol

VTA:

Ventral tegmental area

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Acknowledgments

We are grateful to Ms Suzana Meinhardt for the English revision of the manuscript. DaC, RA, MABFV are recipient of Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)/ Brazil fellowships. This work was supported by grants of Institutos do Milenio (CNPq/MCT), Pronex Paraná, Fundação Araucária, and FAPESP.

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  1. Laboratório de Fisiologia e Farmacologia do Sistema Nervoso Central, Departamento de Farmacologia Universidade Federal do Paraná (UFPR), C.P. 19.031, Centro Politécnico, 81.531-980, Curitiba, PR, Brazil

    Claudio Da Cunha, Evellyn Claudia Wietzikoski, Mariza Bortolanza, Patricia Andréia Dombrowski, Lucélia Mendes dos Santos, Suelen Lúcio Boschen, Maria Aparecida Barbato Frazão Vital, Roseli Boerngen-Lacerda & Roberto Andreatini

  2. Departamento de Ciências Farmacêuticas, Universidade Estadual de Ponta Grossa (UEPG), Av. Carlos Cavalcanti, 4748, 84030-000, Ponta Grossa, PR, Brazil

    Edmar Miyoshi

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    Giuseppe Giovanni

  2. Mario Negri, Istituto di Ricerche Farmacologiche, Via Nazionale 8, Santa Maria Imbaro, 66030, Italy

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    Ennio Esposito

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Da Cunha, C. et al. (2009). Non‐motor Function of the Midbrain Dopaminergic Neurons. In: Giovanni, G., Di Matteo, V., Esposito, E. (eds) Birth, Life and Death of Dopaminergic Neurons in the Substantia Nigra. Journal of Neural Transmission. Supplementa, vol 73. Springer, Vienna. https://doi.org/10.1007/978-3-211-92660-4_12

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