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 (D2+) 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 alpha1-/- mice and pharmacological analysis of tonic currents suggested greater expression of alpha5-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.
Ade
Kristen K
KK
Department of Physiology and Biophysics, Georgetown University School of Medicine, Washington, DC 20007, USA. kka5@georgetown.edu
Janssen
Megan J
MJ
Ortinski
Pavel I
PI
Vicini
Stefano
S
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D003342:Corpus Striatum / Q000166:cytology / Q000502:physiology*; D049229:Dendritic Spines / Q000378:metabolism / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid