Functionally distinct subpopulations of striatal neurons are differentially regulated by GABAergic and dopaminergic inputs--I. In vivo analysis.
Two subpopulations of striatal neurons, Type I and Type II, are distinguished by their contrasting electrophysiological responses to paired impulse stimulation of cortical afferents. Although both Type I and Type II striatal neurons are excited by the first impulse of any pair of impulses, in response to short interstimulus intervals (10-30 ms) Type I neurons display an increase in probability of spike discharge to the second impulse (facilitation), whereas Type II neurons exhibit a decrease in probability of discharge (inhibition); in response to longer interstimulus intervals (50-250 ms) Type I cells display inhibition, whereas Type II cells show facilitation. The present experiments investigated the possibility that the unique paired impulse responses of Type I and Type II neurons reflect differential regulation by GABAergic and dopaminergic afferents. Extracellular recording techniques were combined with micropressure ejection of specific antagonists for GABAA (bicuculline), GABAB (phaclofen), D1 (R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-IH-3-benzazepin+ ++-7-ol; SCH23390) or D2 (sulpiride) receptors; the role of dopamine was also examined using the specific neurotoxin, 6-hydroxydopamine. Results showed that bicuculline (250-500 microM) reduced stimulation threshold for spike discharge of both Type I and Type II neurons and completely antagonized the paired impulse inhibition in response to short interstimulus intervals characteristic of Type II neurons. In contrast, phaclofen (2-30 mM) had only a variable influence on spike threshold for Type II cells and no effect on the paired impulse responses of either Type I or Type II neurons. Micropressure ejection of SCH23390 (1 mM) decreased spike thresholds for both cell types and attenuated the inhibition of spike discharge to long interstimulus intervals distinctive of Type I neurons, an effect which was mimicked by dopaminergic denervation. In contrast, sulpiride (1 mM) had little effect on spike thresholds, and no influence on the paired impulse responses of either cell type. These results indicate that the excitability of both Type I and Type II neurons is tonically inhibited by GABAergic and dopaminergic input via stimulation of GABAA and D1 receptors, respectively. Moreover, the bicuculline sensitivity of Type II neurons suggests that GABAergic input to this cell class arises from neurons within a cortically driven feedforward and/or feedback loop, whereas Type I cells receive input from neurons which lie outside of such a loop. In addition, the inhibition to longer interstimulus intervals characteristic of Type I cells is, at least in part, dependent on dopaminergic input through D1 receptor stimulation.
Nisenbaum
E S
ES
Department of Behavioral Neuroscience, University of Pittsburgh, PA 15260.
Berger
T W
TW
D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D003342:Corpus Striatum / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D004558:Electric Stimulation; D004594:Electrophysiology; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D011963:Receptors, GABA-A / Q000187:drug effects; D013469:Sulpiride / Q000494:pharmacology; D013563:Sympathectomy, Chemical; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000502:physiology*
D001552:Benzazepines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D011963:Receptors, GABA-A; C052329:phaclofen; D005680:gamma-Aminobutyric Acid; D013469:Sulpiride; D001418:Baclofen; D004298:Dopamine; D001640:Bicuculline