4.7 Article

Differential tonic GABA conductances in striatal medium spiny neurons

Journal

JOURNAL OF NEUROSCIENCE
Volume 28, Issue 5, Pages 1185-1197

Publisher

SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3908-07.2008

Keywords

GABA(A) receptors; tonic inhibition; striatum; medium spiny neurons; patch-clamp; chloride channel

Categories

Funding

  1. NIMH NIH HHS [R01 MH64797, R01 MH064797-05, R01 MH064797] Funding Source: Medline

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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.

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