Dopamine modulation of prefrontal cortex interneurons occurs independently of DARPP-32.
Dopamine (DA) exerts a strong influence on inhibition in prefrontal cortex. The main cortical interneuron subtype targeted by DA are fast-spiking gamma-aminobutyric acidergic (GABAergic) cells that express the calcium-binding protein parvalbumin. D1 stimulation depolarizes these interneurons and increases excitability evoked by current injection. The present study examined whether this direct DA-dependent modulation of fast-spiking interneurons involves DARPP-32. Whole-cell patch-clamp recordings were made from fast-spiking interneurons in brain slices from DARPP-32 knockout (KO) mice, wild-type mice, and rats. Low concentrations of DA (100 nM) increased interneuron excitability via D1 receptors, protein kinase A, and cyclic adenosine 3',5'-monophosphate in slices from both normal and DARPP-32 KO mice. Immunohistochemical staining of slices from normal animals revealed a lack of colocalization of DARPP-32 with calcium-binding proteins selective for fast-spiking interneurons, indicating that these interneurons do not express DARPP-32. Therefore, although DARPP-32 impacts cortical inhibition through a previously demonstrated D2-dependent regulation of GABAergic currents in pyramidal cells, it is not involved in the direct D1-mediated regulation of fast-spiking interneurons.
Trantham-Davidson
Heather
H
Medical University of South Carolina, Department of Neuroscience, BSB 403, 173 Ashley Avenue, Charleston, SC 29425, USA.
Kröner
Sven
S
Seamans
Jeremy K
JK
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D064026:Calbindins; D004298:Dopamine / Q000502:physiology*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000235:genetics* / Q000378:metabolism; D007395:Interneurons / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000502:physiology; D009924:Organ Culture Techniques; D010320:Parvalbumins / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000166:cytology* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000502:physiology; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D012559:Schizophrenia / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D015415:Biomarkers; D064026:Calbindins; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D010320:Parvalbumins; C497929:Ppp1r1b protein, mouse; D017447:Receptors, Dopamine D1; D064030:S100 Calcium Binding Protein G; D005680:gamma-Aminobutyric Acid; D004298:Dopamine