Dopamine inhibits GABAA currents in ventral tegmental area dopamine neurons via activation of presynaptic G-protein coupled inwardly-rectifying potassium channels

• Published in: Neuroscience Vol. 165; no. 4; pp. 1159 - 1169
• Main Authors: Michaeli, A, Yaka, R
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 17.02.2010; Elsevier
• Subjects: Biological and medical sciences; disinhibition; dopamine; Fundamental and applied biological sciences. Psychology; GABAA receptor; GIRK; Neurology; psychostimulants; reward circuit; Vertebrates: nervous system and sense organs; VTA; psychostimulants; GABA A receptor; PPD; mIPSC; paired–pulse ratio; reward circuit; artificial cerebrospinal-fluid; GABA receptor type A; evoked-IPSC; GABA receptor type B; barium–chloride; PPR; protein kinase A; GABA AR; G-protein coupled-receptor; PKA; miniature IPSC; BaCl 2; paired-pulse depression; eIPSC; GABA BR; CV; dopamine transporter; ventral tegmental area; regulator of G-protein signaling; DAT; aCSF; G-protein coupled inwardly-rectifying potassium currents; GPCR; GIRK; dopamine; DA; disinhibition; coefficient of variation; RGS; BaCl2; GABAAR; GABABR; GABAA receptor; Dopamine; Central nervous system; Ionic channel; Catecholamine; Encephalon; receptor; Neurotransmitter; GABA; Dopaminergic neuron; Reward; Ventral tegmental area; Potassium; Gabaergic receptor A; Presynaptic neuron; G protein
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2009.11.045

Abstract Dopamine (DA) neurons in the ventral tegmental area (VTA) constitute the origin of major dopaminergic neural pathways associated with essential functions including reward, motivation and cognition. Hence, regulation of VTA DA neurons' excitability is of important significance. Like other neurons, the activity level of VTA DA neurons is considerably determined by excitatory and inhibitory synaptic inputs. Here we show that DA itself, the most available modulator in the VTA, causes an inhibition of GABA receptor type A (GABAA R)-mediated evoked-IPSC (eIPSC) recorded from rat VTA DA neurons. The DA-induced inhibition was accomplished by activation of DA receptors, known to inhibit adenylyl cyclase activity (D2-like receptors), and was absent when these receptors were blocked. Moreover, blocking of either GABA receptor type B (GABAB R) or G-protein coupled inwardly-rectifying potassium (GIRK) channels was also found to effectively prevent the DA-induced inhibition of GABAA R eIPSC. In addition, we found that DA changes the values of both paired-pulse ratio (PPR) and coefficient of variation (CV) of GABAA R eIPSC amplitude, similar to the changes obtained by lowering the extracellular calcium concentration. Taken together, we propose that activation of D2-like receptors and GABAB R in the VTA enhances presynaptic GIRK channels activity, which in turn leads to reduced GABA release. The consequence of reduced GABA release on VTA DA neurons may contribute to their increased activity. Accordingly, a novel potential regulatory form of VTA DA neurons' excitability, which involves presynaptic potassium channels, is proposed.