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

Abstract

Summary 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. While 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.

Role for VGLUT2 in selective vulnerability of midbrain dopamine neurons

“…We then measured optogenetic-evoked excitatory postsynaptic currents (EPSCs) in striatal medium spiny neurons (MSNs) from these cKO mice. As previously reported (9,29,30), cKO mice lack glutamatemediated ChR2-evoked EPSCs, but following AAV-DIO-VGLUT2 expression, we observed 6,7-dinitroquinoxaline-2,3-dione-sensitive (DNQX-sensitive) EPSCs in all cKO MSNs assessed ( Figure 2C). This indicated that the heterologous expression of VGLUT2 is sufficient to endow glutamate release from midbrain DA neurons.…”

Validated multi‐step approach for in vivo recording and analysis of optogenetically evoked glutamate in the mouse globus pallidus

“…; Wang et al . ). In this study, we address the clinically important projection from the STN to the GP and introduce a validated method to perform and analyze enzyme‐based electrochemical recordings of glutamate upon optogenetic stimulation and to correct for artifacts.…”

“…A recent study has provided first evidence for the possibility of measuring optogenetically evoked acetylcholine release (Gritton et al 2016) and we have recently reported the possibility to record glutamate release in the nucleus accumbens following optogenetic stimulation Wang et al 2017). In this study, we address the clinically important projection from the STN to the GP and introduce a validated method to perform and analyze enzyme-based electrochemical recordings of glutamate upon optogenetic stimulation and to correct for artifacts.…”

Dopamine transients delivered in learning contexts do not act as model-free prediction errors

“…In addition, this result allows us to emphasize that our findings do not contradict the many other roles that dopamine has been shown to play when delivered for longer time periods or in situations less structured or constrained to isolate associative learning. Indeed, direct activation of dopamine neurons outside of a learning context clearly produces a motivation and behavioral drive that could be called value 7,[27][28][29][30][31][32] . In fact, it has recently been shown that directly pairing a cue with optogenetic activation of dopamine neurons, many times and without an obvious external precipitating event,…”