Bursting in substantia nigra pars reticulata neurons in vitro: possible relevance for Parkinson disease.
Projection neurons of the substantia nigra reticulata (SNr) convey basal ganglia (BG) processing to thalamocortical and brain stem circuits responsible for movement. Two models try to explain pathological BG performance during Parkinson disease (PD): the rate model, which posits an overexcitation of SNr neurons due to hyperactivity in the indirect pathway and hypoactivity of the direct pathway, and the oscillatory model, which explains PD as the product of pathological pattern generators disclosed by dopamine reduction. These models are, apparently, incompatible. We tested the predictions of the rate model by increasing the excitatory drive and reducing the inhibition on SNr neurons in vitro. This was done pharmacologically with bath application of glutamate agonist N-methyl-d-aspartate and GABA(A) receptor blockers, respectively. Both maneuvers induced bursting behavior in SNr neurons. Therefore synaptic changes forecasted by the rate model induce the electrical behavior predicted by the oscillatory model. In addition, we found evidence that Ca(V)3.2 Ca(2+) channels are a critical step in generating the bursting firing pattern in SNr neurons. Other ion channels involved are: hyperpolarization-activated cation channels, high-voltage-activated Ca(2+) channels, and Ca(2+)-activated K(+) channels. However, although these channels shape the temporal structure of bursting, only Ca(V)3.2 Ca(2+) channels are indispensable for the initiation of the bursting pattern.
Ibáñez-Sandoval
Osvaldo
O
Departamento de Biofísica, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México City, México.
Carrillo-Reid
Luis
L
Galarraga
Elvira
E
Tapia
Dagoberto
D
Mendoza
Ernesto
E
Gomora
Juan C
JC
Aceves
Jorge
J
Bargas
José
J
D000818:Animals; D001479:Basal Ganglia / Q000166:cytology / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003627:Data Interpretation, Statistical; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D008959:Models, Neurological; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D010300:Parkinson Disease / Q000503:physiopathology*; D018408:Patch-Clamp Techniques; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013378:Substantia Nigra / Q000166:cytology / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D002121:Calcium Channel Blockers; D018691:Excitatory Amino Acid Antagonists; D007473:Ion Channels; D024681:Potassium Channels, Calcium-Activated; D016194:Receptors, N-Methyl-D-Aspartate; D013757:Tetraethylammonium Compounds