Collocalisation of neurotransmitters

Different types of neurons are generally distinguished from one another by one or more salient properties – their location in the brain (e.g. thalamic interneurons); their shape (medium spiny neurons); their activity (fast spiking neurons); or the neurotransmitter they release (e.g. dopaminergic neurons).

Although traditionally neurons were considered to release only one neurontransmitter, there is increasing evidence that some neurons can release multiple neurotransmitters. Part of the evidence has been different types cellular machinery needed to produce different neurotransmitters were found in the same cell. This could have been a biological accident – proteins for production of the ‘wrong’ neurotransmitter being made in error. However, if this behaviour was accidental, I’d expect it to happen either uniformly or randomly throughout the brain. What I wouldn’t expect from an accidental process is a selective pattern of distribution. But this is what we find.

Some of the networks in the brain rely on coordinated signals transmitted by relase of dopamine and glutamate, and some dopaminergic neurons have been shown to also release glutamate. However, the prodcess isn’t well understood. A paper from researchers at UCSF demonstrates that only a select population of dopamine neurons of the midbrain also release glutamate – those that project to the shell of the nucleus accumbens, but not those that project to the dorsal striatum. Researchers used optogenetic techniques to make neurons that released glutamate light sensitive. When neurons that were identified as dopaminergic were stimulated with light, only those that projected to the shell of the nucleus accumbens released glutamate. The release of glutamate was detected by recording the activity of neurons in the nucleus accumbens and dorsal striatum that are usually sensitive to glutamate, called medium spiny neurons (MSNs). When the dopamine neurons were stimulated with light, the MSNs activity increased. The change in activity wasn’t seen when a drug was applied that blocks the effect of glutamate on MSNs. The effect also wasn’t seen in genetically modified mice that lacked a part of the cellular machinery that produces and releases glutamate.

Confirmation that neurons can release multiple neurotransmitters is important in itself. However, this study raises more issues. The ability of neurons to activate both glutamate and dopamine receptive neurons has implications for the ability to respond to salient/rewarding/pleasant stimuli. However, the lack of this ability in the dorsal striatum, which receives substantial glutamate input from other regions of the brain is also interesting – does glutamate corelease from dopamine neurons in the nucleus accumbens serve a similar function to glutamate release in the dorsal striatum from elsewhere, or is it unreleated?

Stuber GD, Hnasko TS, Britt JP, Edwards RH, & Bonci A (2010). Dopaminergic terminals in the nucleus accumbens but not the dorsal striatum corelease glutamate. The Journal of neuroscience : the official journal of the Society for Neuroscience, 30 (24), 8229-33 PMID: 20554874