Presynaptic inhibition by dopamine of a discrete component of GABA release in rat substantia nigra pars reticulata

摘要

class="enumerated" style="list-style-type:decimal">Whole-cell patch clamp recordings were made from substantia nigra pars reticulata (SNr) neurones in rat midbrain slices. Monosynaptic IPSCs were evoked by electrical stimulation of the cerebral peduncle in the presence of the glutamate receptor antagonists CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) and AP5 (2-amino-5-phosphonopentanoic acid).IPSCs were predominantly outward at −70 mV (in 124/135 cells), with a reversal potential of −83 mV, a time to peak of 2.6 ms and a decay time constant of 6.5 ms. Faster inward IPSCs were also observed in thirty-five cells, with a time to peak of 1.0 ms, a decay time constant of 2.3 ms, and a reversal potential of −61 mV. Both IPSCs were sensitive to the GABAA receptor antagonists picrotoxin or bicuculline.In cells recorded with Cs⁺-filled pipettes, the outward IPSC reversal potential was shifted to −76 mV, closer to the estimated Cl⁻ equilibrium potential of −56 mV, while that of the inward IPSC was unchanged at −64 mV.The outward IPSC was reversibly depressed by up to 100 % by dopamine in a concentration-dependent manner with an IC50 of 10.5 μm, while the inward IPSC was relatively insensitive.Dopamine was without effect on cell holding current, or on outward IPSC reversal potential, but it increased paired-pulse IPSC facilitation, consistent with a presynaptic site of action.The D1-like dopamine receptor agonist SKF 38393 (10 μm) depressed the outward IPSC by 43 %, while the D2-like dopamine receptor agonist quinpirole (10 μm) was without effect.It is concluded that GABA-ergic synaptic input onto distal rather than proximal regions of SNr neurones is susceptible to presynaptic inhibition via a D1-like receptor. These inputs are probably from striato-nigral fibres, and their inhibition by dopamine is likely to influence the patterning of basal ganglia output.