Differential tonic GABA conductances in striatal medium spiny neurons

Medium spiny neurons (MSNs) provide the principal output for the dorsal striatum. Those that express dopamine D-2 receptors (D-2(+)) project to the globus pallidus external and are thought to inhibit movement, whereas those that express dopamine D-1 receptors (D-1(+)) project to the substantia nigra pars reticulata and are thought to facilitate movement. Whole-cell and outside-out patch recordings in slices from bacterial artificial chromosome transgenic mice examined the role of GABA(A) receptor-mediated currents in dopamine receptor D-1(+) striatonigral and D-2(+) striatopallidal MSNs. Although inhibitory synaptic currents were similar between the two neuronal populations, D-2(+) MSNs showed greater GABA(A) receptor-mediated tonic currents. TTX application abolished the tonic current to a similar extent as GABAA antagonists, suggesting a synaptic origin of the ambient GABA. Low GABA concentrations produced larger whole-cell responses and longer GABA channel openings in D-2(+) than in D-1(+) MSNs. Recordings from MSNs in alpha 1(-/-) mice and pharmacological analysis of tonic currents suggested greater expression of alpha 5-containing GABA(A) receptors in D-2(+) than in D-1(+) MSNs. As a number of disorders such as Parkinson's disease, Huntington's chorea, and tardive dyskinesia arise from an imbalance between these two pathways, the GABA(A) receptors responsible for tonic currents in D-2(+) MSNs may be a potential target for therapeutic intervention.