Functionally distinct subpopulations of striatal neurons are differentially regulated by gabaergic and dopaminergic inputs—I. In vivo analysis

Abstract In the companion report [ Nisenbaum and Berger (1992) Neuroscience48, 561–578] the contrasting paired impulse responses to stimulation of the corticostriatal pathway which define the Type I and Type II subpopulations of striatal neurons were shown to reflect differential regulation by GABAergic and dopaminergic inputs. More specifically, the decreased probability of spike discharge (inhibition) to long interstimulus intervals (60–260 ms) characteristic of Type I neurons was found to be dependent on dopaminergic input via D1 receptor activation, whereas the inhibition to short interstimulus intervals (10–20 ms) distinctive of Type II neurons was found to be mediated by GABAergic input acting through GABAA receptor stimulation. The present experiments have further investigated the contribution of GABAergic and dopaminergic feedforward and/or feedback circuits to the functional identities of Type I and Type II neurons using an in vitro corticostriatal slice preparation. In this preparation, the cortical afferents to the striatum are preserved, allowing for activation of striatal cells in a manner similar to that used in vivo; however, all axons arising from midbrain and brainstem structures including the substantia nigra are transected, and intrastriatal GABAergic pathways are reduced. Consistent with the predicted effect of disrupting these two neurotransmitter pathways, the paired impulse responses of striatal neurons recorded in vitro were not similar to the responses of either Type I or Type II neurons recorded in vivo. Indeed, the paired impulse profiles of striatal neurons recorded in vitro were relatively homogeneous in that virtually all cells displayed an increased probability of spike discharge (facilitation) to the second impulse of all interstimulus intervals (10–500 ms) tested. Low concentrations of allosteric agonists for the GABAA receptor, pregnanolone (5 μM) and pentobarbital (50 μM), selectively inhibited spike discharge in response to short interstimulus intervals (10–20 ms) for approximately 40% of the neurons sampled, but produced no change in facilitation to longer interstimulus intervals (30–500 ms). The agonist-induced inhibition to short interstimulus intervals was blocked by bicuculline (10–20 μM), and was not mimicked by the GABAB receptor agonist, baclofen (1–5 μM). In addition, application of dopamine (5–10 μM) or the D1 receptor agonist, SKF38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; 5 μM), inhibited spike discharge to longer interstimulus intervals (40–500 ms) for approximately 10% of striatal cells recorded. The inhibition to longer interstimulus intervals was blocked by the D1 receptor antagonist, SCH23390 [ R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol], but not the D2 antagonist, sulpiride. Finally, when both GABAergic and dopaminergic inputs were enhanced simultaneously by application of pregnanolone (5 μM) and dopamine (5 μM), separate populations of striatal neurons displaying either Type I- or Type II-like paired impulse response profiles were identified. In summary, these results define pharmacological conditions for which Type I- and Type II-like paired impulse profiles can be detected in vitro, as well as provide further evidence for the dependence of the short-interstimulus interval inhibition of Type II cells on GABAA receptor stimulation and the reliance of the long-interstimulus interval inhibition of Type I neurons on D1 receptor activation.