Neurochemical signaling of reward and aversion by ventral tegmental area glutamate neurons

Ventral tegmental area (VTA) glutamate neurons signal and participate in reward and aversion-based behaviors. However, the neurochemical mechanisms that underlie how these neurons participate in diverse motivated behaviors is unknown. We used a combination of optical sensors to identify how distinct neurochemical inputs to VTA glutamate neurons participate in motivated behavior. Glutamate inputs to VTA glutamate neurons increased for both reward- and aversion-predicting cues and aversive outcomes, but subpopulations of glutamate inputs were increased or decreased by reward. For all cues and outcomes, GABA inputs to VTA glutamate neurons decreased and GCaMP-measured neuronal activity increased. GCaMP recordings also showed that VTA glutamate neuronal activity discriminated between the omission and receipt of an expected reward, but glutamate and GABA inputs to these neurons did not. Electro-physiological recordings in coordination with our sensor data suggest that glutamate inputs, but not GABA inputs, principally regulate VTA glutamate neuron participation in diverse motivated behaviors.