Disrupting Glutamate Co-transmission Does Not Affect Acquisition of Conditioned Behavior Reinforced by Dopamine Neuron Activation

Dopamine neurons in the ventral tegmental area (VTA) were previously found to express vesicular glutamate transporter 2 (VGLUT2) and to co-transmit glutamate in the ventral striatum (VStr). This capacity may play an important role in reinforcement learning. Although it is known that activation of the VTA-VStr dopamine system readily reinforces behavior, little is known about the role of glutamate co-transmission in such reinforcement. By combining electrode recording and optogenetics, we found that stimulation of VTA dopamine neurons in vivo evoked fast excitatory responses in many VStr neurons of adult mice. Whereas conditional knockout of the gene encoding VGLUT2 in dopamine neurons largely eliminated fast excitatory responses, it had little effect on the acquisition of conditioned responses reinforced by dopamine neuron activation. Therefore, glutamate co-transmission appears dispensable for acquisition of conditioned responding reinforced by DA neuron activation. [Display omitted] •Glutamate co-release from DA neurons drives fast excitatory responses in VStr in vivo•Loss of VGLUT2 in DA neurons abolishes glutamate co-transmission•Such loss does not disrupt DA neurons from reinforcing behavior Wang et al. find that targeted deletion of the gene encoding VGLUT2 in dopamine neurons largely eliminates fast excitatory responses caused by glutamate co-transmission in the ventral striatum in vivo. However, it has little effect on the acquisition of conditioned responses reinforced by the activation of VTA dopamine neurons.