Electrophysiological and Morphological Evidence for a GABAergic Nigrostriatal Pathway

• Published in: The Journal of neuroscience Vol. 19; no. 11; pp. 4682 - 4694
• Main Authors: Rodriguez, Manuel, Gonzalez-Hernandez, Tomas
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 01.06.1999; Society for Neuroscience
• Subjects: Animals; Brain Mapping; Corpus Striatum - cytology; Corpus Striatum - physiology; Dopamine - physiology; gamma-Aminobutyric Acid - physiology; Male; Nerve Degeneration; Neural Pathways - physiology; Neurons - physiology; Rats; Rats, Sprague-Dawley; Substantia Nigra - cytology; Substantia Nigra - physiology
• ISSN: 0270-6474; 1529-2401; 1529-2401
• DOI: 10.1523/JNEUROSCI.19-11-04682.1999

The electrophysiological and neurochemical characteristics of the nondopaminergic nigrostriatal (NO-DA) cells and their functional response to the degeneration of dopaminergic nigrostriatal (DA) cells were studied. Three different criteria were used to identify NO-DA cells: (1) antidromic response to striatal stimulation with an electrophysiological behavior (firing rate, interspike interval variability, and conduction velocity) different from that of DA cells; (2) retrograde labeling after striatal injection of HRP but showing immunonegativity for DA cell markers (tyrosine hydroxylase, calretinin, calbindin-D28k, and cholecystokinin); and (3) resistance to neurotoxic effect of 6-hydroxydomine (6-OHDA). Our results showed that under normal conditions, 5–8% of nigrostriatal neurons are immunoreactive for GABA, glutamic acid decarboxylase, and parvalbumin, markers of GABAergic neurons, a percentage that reached 81–84% after 6-OHDA injection. Electrophysiologically, NO-DA cells showed a behavior similar to that found in other nigral GABAergic (nigrothalamic) cells. In addition, the 6-OHDA degeneration of DA cells induced a modification of their electrophysiological pattern similar to that found in GABAergic nigrothalamic neurons. Taken together, the present data indicate the existence of a small GABAergic nigrostriatal pathway and suggest their involvement in the pathophysiology of Parkinson’s disease.