TY - JOUR
T1 - Differential tonic GABA conductances in striatal medium spiny neurons
AU - Ade, Kristen K.
AU - Janssen, Megan J.
AU - Ortinski, Pavel I.
AU - Vicini, Stefano
PY - 2008/1/30
Y1 - 2008/1/30
N2 - 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 GABAA 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 GABAA 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 D2 + than in D1+ MSNs. Recordings from MSNs in α1-/- mice and pharmacological analysis of tonic currents suggested greater expression of α5-containing GABAA 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.
AB - 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 GABAA 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 GABAA 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 D2 + than in D1+ MSNs. Recordings from MSNs in α1-/- mice and pharmacological analysis of tonic currents suggested greater expression of α5-containing GABAA 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.
KW - Chloride channel
KW - GABA receptors
KW - Medium spiny neurons
KW - Patch-clamp
KW - Striatum
KW - Tonic inhibition
UR - http://www.scopus.com/inward/record.url?scp=38749134113&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38749134113&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.3908-07.2008
DO - 10.1523/JNEUROSCI.3908-07.2008
M3 - Article
C2 - 18234896
AN - SCOPUS:38749134113
SN - 0270-6474
VL - 28
SP - 1185
EP - 1197
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 5
ER -