RT Journal Article SR Electronic T1 Attenuating GABAA Receptor Signaling in Dopamine Neurons Selectively Enhances Reward Learning and Alters Risk Preference in Mice JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 17103 OP 17112 DO 10.1523/JNEUROSCI.1715-11.2011 VO 31 IS 47 A1 Jones G. Parker A1 Matthew J. Wanat A1 Marta E. Soden A1 Kinza Ahmad A1 Larry S. Zweifel A1 Nigel S. Bamford A1 Richard D. Palmiter YR 2011 UL http://www.jneurosci.org/content/31/47/17103.abstract AB Phasic dopamine (DA) transmission encodes the value of reward-predictive stimuli and influences both learning and decision-making. Altered DA signaling is associated with psychiatric conditions characterized by risky choices such as pathological gambling. These observations highlight the importance of understanding how DA neuron activity is modulated. While excitatory drive onto DA neurons is critical for generating phasic DA responses, emerging evidence suggests that inhibitory signaling also modulates these responses. To address the functional importance of inhibitory signaling in DA neurons, we generated mice lacking the β3 subunit of the GABAA receptor specifically in DA neurons (β3-KO mice) and examined their behavior in tasks that assessed appetitive learning, aversive learning, and risk preference. DA neurons in midbrain slices from β3-KO mice exhibited attenuated GABA-evoked IPSCs. Furthermore, electrical stimulation of excitatory afferents to DA neurons elicited more DA release in the nucleus accumbens of β3-KO mice as measured by fast-scan cyclic voltammetry. β3-KO mice were more active than controls when given morphine, which correlated with potential compensatory upregulation of GABAergic tone onto DA neurons. β3-KO mice learned faster in two food-reinforced learning paradigms, but extinguished their learned behavior normally. Enhanced learning was specific for appetitive tasks, as aversive learning was unaffected in β3-KO mice. Finally, we found that β3-KO mice had enhanced risk preference in a probabilistic selection task that required mice to choose between a small certain reward and a larger uncertain reward. Collectively, these findings identify a selective role for GABAA signaling in DA neurons in appetitive learning and decision-making.