Congratulations to Dillon and collaborator Abby Polter on their preprint: Neurochemical signaling of reward and aversion by ventral tegmental area glutamate neurons. Download it here.
We previously found that subsets of VTA glutamate neurons either increase or decrease firing at reward but most are activated by aversive stimuli (paper here). Here, Dillon aimed to identify the neurochemical inputs to VTA glutamate neurons that contribute to these diverse motivation-related responses. He used new optical sensors of glutamate or GABA inputs specifically to VTA glutamate neurons during motivated behaviors. You can find them on Addgene as SF-iGluSnFR and iGABASnFR, developed by Jonny Marvin in the Looger lab.
We found that while glutamate inputs increased at reward-related cues, subpopulations of glutamate inputs either increased or decreased following reward. The reward-related glutamate responses mirror our prior electrophysiological results of VTA glutamate neurons that increase or decrease firing at reward. GABA inputs to VTA glutamate neurons decreased following reward-related cues and events.
Regardless of their reward-related response, glutamate inputs increase following aversion-related cues and events. This strong and reliable glutamatergic drive to VTA glutamate neurons by aversion-related stimuli likely underlies our observation that most VTA glutamate neurons increase firing by aversive events. In response to aversive cues and events, GABA inputs decrease.
We compared the neurotransmitter sensor responses to those of GCaMP and found some interesting differences. We believe that the use of neurotransmitter sensors is complimentary to neuronal activity-based sensors. The neurotransmitter sensors offer the unique opportunity to investigate the neurochemical inputs that may relay certain behavior-relevant events that are integrated into a coherent neuronal response measured by GCaMP (or other sensor).
Finally, Abby examined how glutamate and GABA receptors affect the firing of VTA glutamate neurons. Glutamate receptors control the spontaneous firing of these neurons but GABA-A receptors are surprisingly not very effective in changing their spontaneous firing. Together, we hypothesize that 1) fluctuating levels of glutamate inputs excite or disexcite VTA glutamate neurons during their signaling of motivated behaviors and that 2) different glutamatergic circuits control VTA glutamate neuron participation in reward or aversion-based behaviors.
