Original Research ARTICLE
Dopaminergic presynaptic modulation of nigral afferents: its role in the generation of recurrent bursting in substantia nigra pars reticulata neurons
- División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Distrito Federal México, México
Previous work has shown the functions associated with activation of dopamine presynaptic receptors in some substantia nigra pars reticulata (SNr) afferents: (i) striatonigral terminals (direct pathway) posses presynaptic dopamine D1-class receptors whose action is to enhance inhibitory postsynaptic currents (IPSCs) and GABA transmission. (ii) Subthalamonigral terminals posses D1- and D2-class receptors where D1-class receptor activation enhances and D2-class receptor activation decreases excitatory postsynaptic currents. Here we report that pallidonigral afferents posses D2-class receptors (D3 and D4 types) that decrease inhibitory synaptic transmission via presynaptic modulation. No action of D1-class agonists was found on pallidonigral synapses. In contrast, administration of D1-receptor antagonists greatly decreased striatonigral IPSCs in the same preparation, suggesting that tonic dopamine levels help in maintaining the function of the striatonigral (direct) pathway. When both D3 and D4 type receptors were blocked, pallidonigral IPSCs increased in amplitude while striatonigral connections had no significant change, suggesting that tonic dopamine levels are repressing a powerful inhibition conveyed by pallidonigral synapses (a branch of the indirect pathway). We then blocked both D1- and D2-class receptors to acutely decrease direct pathway (striatonigral) and enhance indirect pathways (subthalamonigral and pallidonigral) synaptic force. The result was that most SNr projection neurons entered a recurrent bursting firing mode similar to that observed during Parkinsonism in both patients and animal models. These results raise the question as to whether the lack of dopamine in basal ganglia output nuclei is enough to generate some pathological signs of Parkinsonism.
Keywords: basal ganglia, striatum, substantia nigra pars reticulata, dopamine function, striatonigral synapses, pallidonigral synapses, D1-receptors, D2-receptors
Citation: Aceves JJ, Rueda-Orozco PE, Hernández R, Plata V, Ibañez-Sandoval O, Galarraga E and Bargas J (2011) Dopaminergic presynaptic modulation of nigral afferents: its role in the generation of recurrent bursting in substantia nigra pars reticulata neurons. Front. Syst. Neurosci. 5:6. doi: 10.3389/fnsys.2011.00006
Received: 15 December 2010;
Paper pending published: 04 January 2011;
Accepted: 23 January 2011; Published online: 10 February 2011.
Edited by:James M. Tepper, Rutgers, The State University of New Jersey, USA
Reviewed by:Christian Lee, New York University School of Medicine, USA
Carlos A. Paladini, University of Texas at San Antonio, USA
Copyright: © 2011 Aceves, Rueda-Orozco, Hernández, Plata, Ibañez-Sandoval, Galarraga and Bargas. This is an open-access article subject to an exclusive license agreement between the authors and Frontiers Media SA, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.
*Correspondence: José Bargas, Division of Neuroscience, Institute of Cell Physiology, Universidad Nacional Autónoma de México, PO Box: 70-253, Distrito Federal México 04510, México. e-mail: email@example.com