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 D₂ receptors (D ₂⁺) project to the globus pallidus external and are thought to inhibit movement, whereas those that express dopamine D₁ receptors (D₁⁺) 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 D₁⁺ striatonigral and D₂⁺ striatopallidal MSNs. Although inhibitory synaptic currents were similar between the two neuronal populations, D₂⁺ MSNs showed greater GABA_A receptor-mediated tonic currents. TTX application abolished the tonic current to a similar extent as GABA_A antagonists, suggesting a synaptic origin of the ambient GABA. Low GABA concentrations produced larger whole-cell responses and longer GABA channel openings in D₂ ⁺ than in D₁⁺ MSNs. Recordings from MSNs in α1^-/- mice and pharmacological analysis of tonic currents suggested greater expression of α5-containing GABA_A receptors in D₂⁺ than in D₁⁺ 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 D₂ ⁺ MSNs may be a potential target for therapeutic intervention.