Abstract
The dopaminergic neurons of the ventral tegmental area (VTA) have been identified with the ability to co-release dopamine and glutamate. This ability was first documented in the nucleus accumbens but showed to be absent in the dorsal striatum. Recently the ability to release glutamate from a subpopulation of the VTA dopaminergic neurons has been shown to control the prefrontal cortex (PFC) excitation through the exclusive innervation of GABAergic fast spiking interneurons. Here, using an optogenetic approach, we expand this view by presenting that the VTA dopaminergic neurons do not only innervate interneurons but also pyramidal PFC neurons. This finding opens the range of possibilities for the VTA dopaminergic neurons to modulate the activity of PFC.
Highlights
The first data documenting the co-release of dopamine and glutamate by dopaminergic neurons dates back to 1998, when it was shown in cell cultures that dopaminergic neurons from the midbrain had the ability to release glutamate at their axonal terminals (Sulzer et al, 1998; Joyce and Rayport, 2000)
It was demonstrated that the selective deletion of vesicular glutamate transporter type 2 (VGluT2) in dopaminergic neurons eliminated the ability of ventral tegmental area (VTA) dopaminergic neurons to release glutamate, showing that the VGluT2 participated in the release of glutamate from dopaminergic cells (Fortin et al, 2012; Hnasko et al, 2012)
The quantification of eYFP+/TH+ fibers and cell bodies in randomly selected Z-stacks of the prefrontal cortex (PFC) and all cells transfected in the VTA (n = 3 animals) showed the specificity of the FI12:THCre for targeting the cell bodies of VTA dopaminergic neurons was 96.32% (Figure 1E)
Summary
The first data documenting the co-release of dopamine and glutamate by dopaminergic neurons dates back to 1998, when it was shown in cell cultures that dopaminergic neurons from the midbrain had the ability to release glutamate at their axonal terminals (Sulzer et al, 1998; Joyce and Rayport, 2000). Due to the nature of extracellular stimulation (it can activate fibers of passage), the selective activation of the VTA dopaminergic axons only came from the optogenetic activation of VTA axons expressing Channelrhodopsin-2 (ChR2; Stuber et al, 2010; Tecuapetla et al, 2010) In these experiments photo-activation of VTA dopaminergic axons in the nucleus accumbens evoked the release of glutamate in adult animals. When similar optogenetic experiments were performed to evaluate whether the dopaminergic neurons released glutamate in the dorsal striatum, this release was not observed (Stuber et al, 2010) This last finding provided evidence that not all post-synaptic targets of the dopaminergic neurons receive the co-release of dopamine-glutamate.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
