With the advanced neuroscience techniques available to elucidate mechanisms today, neuroscientists are beginning to re-define  a classically basic neuroscience principle: one neuron type releases only one type of neurotransmitter. Within the past few months, most of which has been published in The Journal of Neuroscience, there is convincing evidence that the central reward circuit co-releases both dopamine and glutamate. I’m talking, of course, about the ventral tegmental area (VTA) of the pons and the nucleus accumbens (NA) of the forebrain. Though there are other structures largely involved with processing general reward, such as the striatum, so far, there’s no evidence that there is co-release of dopamine and glutamate within striatal pathways (looking specifically at connections to/from the substantia nigra, a dopamine-enriched region, and the globus pallidus, which is a constituent of the striatum).

I have reported about the experimental details of this particular article in July, but one of the authors provided a brief summary of the research and recent progress related to the experiments in this week’s Journal of Neuroscience.  He also provided a wonderful schematic detailing the eight possible scenarios involving pre and post-synaptic neurons, ResearchBlogging.orgnon-synaptic neurons (varicosities), and receptor/transport subtypes that could explain the co-release of dopamine and glutamate. For now, we know that EPSCs (excitatory post-synaptic currents) are elicited by both dopamine and glutamate in the VTA and NA. This was accomplished through exploiting channel rhodopsin. In the absence of VGLUT (a vesicular glutamate transporter) these EPSCs did not occur. Additionally, glutamate binding to AMPA receptors (glutamate can either bind to AMPA or NMDA receptors) was found in the NA.

Regarding my own research, this recent progress will be a nice complement to my experiments showing that the implantation of the glutamate antagonist, acamprosate, which is used to curb drinking and prevent relapse in alcoholics, into the VTA and NA effectively reduces alcohol craving in mice. Implantation into the VTA also causes a marked increase in nighttime circadian activity. As you can see here. I certainly need to do some more literature searching, looking for experiments tying dopamine/glutamate signaling to changes in circadian behavior, but for now, I have to return to my week-long immunohistochemistry/surgical duties………

Gu XL (2010). Deciphering the corelease of glutamate from dopaminergic terminals derived from the ventral tegmental area. The Journal of neuroscience : the official journal of the Society for Neuroscience, 30 (41), 13549-51 PMID: 20943895