Response of the GABAergic and dopaminergic mesostriatal projections to the lesion of the contralateral dopaminergic mesostriatal pathway in the rat

Authors

  • Tomás González-Hernández MD, PhD,

    Corresponding author
    1. Departamento de Anatomía, Universidad de La Laguna, La Laguna, Tenerife, Spain
    • Departamento de Anatomía, Facultad de Medicina, Universidad de La Laguna, La Laguna, Tenerife, Spain
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  • Pedro Barroso-Chinea,

    1. Departamento de Anatomía, Universidad de La Laguna, La Laguna, Tenerife, Spain
    2. Unidad de Investigación, Hospital Universitario de Canarias, La Laguna, Tenerife, Spain
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  • Manuel Rodríguez MD, PhD

    1. Departamento de Fisiología, Universidad de La Laguna, La Laguna, Tenerife, Spain
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Abstract

Although dopamine is the main neurotransmitter in the mesostriatal system, recent studies indicate the existence of two nigrostriatal GABAergic projections: one arising from neurons immunoreactive for GABA, glutamic acid decarboxylase (GAD67), and parvalbumin (PV) lying in the substantia nigra pars reticulata (nigrostriatal GABA cells) and the other arising from a subpopulation of dopaminergic neurons lying in the substantia nigra pars compacta and ventral tegmental area, which under normal conditions, contains mRNA for GAD65 (one of the two isoforms of glutamic acid decarboxylase), but which is not immunoreactive for GABA and GAD65 (nigrostriatal dopaminergic [DA]/GABA cells). With the aim of improving our knowledge about the interaction between the nigrostriatal system of both brain hemispheres, we have studied the response of these three components of the mesostriatal system (GABA, DA/GABA, and DA) to the lesion of the contralateral mesostriatal DA pathway, by using morphological and neurophysiological techniques. Our findings show that, in the side contralateral to the lesion, (1) the number of nigrostriatal GABA cells increases from 6% to 17% with respect to the total number of nigrostriatal cells, (2) the soma of DA/GABA cells becomes immunoreactive for GABA and GAD65, and (3) there is an increase in the firing rate and burst activity of DA-neurons, except in those projecting to the striatum, which may be under the action of the GABA hyperactivity. Taken together, our results suggest that the GABAergic components of the mesostriatal projection play a regulatory role on the DA component, activated or upregulated after contralateral DA lesion and are probably addressed to restoring the functional symmetry in basal ganglia and to slowing down the contralateral progression of DA-cell degeneration in Parkinson's disease. © 2004 Movement Disorder Society

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