In vivo release of newly synthesized [3H]GABA in the substantia nigra of the rat: relative contribution of GABA striato-pallido-nigral afferents and nigral GABA neurons.
The release of [3H]gamma-aminobutyric acid ([3H]GABA) continuously formed from [3H]glutamine has been measured with a push-pull cannula implanted in the substantia nigra of the rat anesthetized with ketamine. Consistent with the high density of GABA terminals coming from both the striato-pallido-nigral afferents, and from GABA nigrofugal neurons, our results showed that a large amount of [3H]GABA was spontaneously released in the reticulata, about 4 times higher than in the compacta. In the absence of calcium the spontaneous [3H]GABA release was reduced (-30%), as well as the K(+)-induced release of [3H]GABA (-66%). Bicuculline (10(-4) M) did not affect the K(+)-evoked release of [3H]GABA, suggesting that autoreceptors on GABA afferent fibers are distinct from the GABAA subtype. Partial lesions of striato- and pallido-nigral GABA neurons with kainic acid (1.2 micrograms) decrease by 40% the glutamic acid decarboxylase (GAD) activity in the ipsilateral SN without decreasing the spontaneous release of [3H]GABA; even following extensive lesions with kainic acid (2.5 micrograms), GAD activity (-72%) and spontaneous [3H]GABA release (-83%) were not completely abolished. These results suggest that a non-negligible contribution of GABA nigral neurons accounts for the spontaneous GABA release measured in the substantia nigra. This is further supported by the decrease (-20%), and the increase (+40%) of [3H]GABA release produced by the local application of glycine (10(-6) M), and bicuculline (10(-4) M), which respectively, inhibits and activates the nigral neuron activity. The contribution of nigral GABA neurons to the amount of [3H]GABA release from the substantia nigra, is likely linked to their high spontaneous firing rate.
Lantin le Boulch
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Laboratoire de Neurochimie Anatomie, C.N.R.S., Université Pierre et Marie Curie, Paris, France.
Truong-Ngoc
N A
NA
Gauchy
C
C
Besson
M J
MJ
D000758:Anesthesia; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D003342:Corpus Striatum / Q000502:physiology*; D005917:Globus Pallidus / Q000502:physiology*; D005973:Glutamine / Q000378:metabolism; D005998:Glycine / Q000494:pharmacology; D007608:Kainic Acid / Q000633:toxicity; D007649:Ketamine; D008297:Male; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013238:Stereotaxic Techniques; D013378:Substantia Nigra / Q000378:metabolism* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis* / Q000502:physiology
D005973:Glutamine; D005680:gamma-Aminobutyric Acid; D007649:Ketamine; D011188:Potassium; D007608:Kainic Acid; D002118:Calcium; D005998:Glycine; D001640:Bicuculline