Dopamine and GABA working together

Until recently, the neurotransmitters of the brain have thought to be generally separate. That is, if a neuron is inhibitory, it releases GABA, and if it is neuromodulatory, it releases something else, dopamine perhaps.  But two new papers show that specific neurons release both GABA and Dopamine. I briefly mention these new findings here.

Dopamine and GABA together forever (source)

First a subset of cells that were mainly thought to be GABAergic turn out to release dopamine as well. In 2010, Ibanez-Sandoval et al. found that there are interneurons in the striatum that stain positive for Tyrosine Hydroxylase. Tyrosine Hydroxylase is a precursor molecule needed for the creation of dopamine, and is a telltale sign of a neuron that can make and release dopamine. The authors found that these neurons release GABA and inhibit nearby cells. In this paper they did not confirm that the cells actually release dopamine, just that they have the machinery for it.

This is weird for a few reasons. 1. Why would the striatum need dopamine in its interneurons? The main source of dopamine to this brain region is the substantia nigra pars compacta, and it pretty well covers the entire striatum with dopamine when it wants to. 2. Why would a cell release dopamine and GABA at the same time?  

Second the canonical dopaminergic neurons of the substantia nigra turn out to release GABA as well. In 2012, Tritsch et al., found that when stimulated with light, the dopaminergic neurons of the substantia nigra cause inhibitory responses in the cells in the striatum.

The authors did extensive control experiments to make sure that they were indeed seeing GABA release from dopaminergic axons. They used carbon fiber amperometry to measure dopamine, and confirmed that dopamine was being released, and they blocked GABA receptors to make sure that it was GABA that was causing the inhibitory response. Finally they tested whether these cells were directly releasing GABA or perhaps stimulating other cells that released GABA. They did this by adding TTX, a sodium channel blocker, to prevent action potentials. In this condition, they could still evoke neurotransmitter release by light-based activation of these axons, confirming that these neurons directly release both dopamine and GABA.

So what's with this mash up?

Within two years it's been shown that GABA cells might release dopamine and dopamine cells do release GABA. Why? Neither paper speculates much on why GABA and dopamine might be co-released, or what the consequences of such a partnership might be.

© TheCellularScale


Ibáñez-Sandoval O, Tecuapetla F, Unal B, Shah F, Koós T, & Tepper JM (2010). Electrophysiological and morphological characteristics and synaptic connectivity of tyrosine hydroxylase-expressing neurons in adult mouse striatum. The Journal of neuroscience : the official journal of the Society for Neuroscience, 30 (20), 6999-7016 PMID: 20484642

Tritsch NX, Ding JB, & Sabatini BL (2012). Dopaminergic neurons inhibit striatal output through non-canonical release of GABA. Nature, 490 (7419), 262-6 PMID: 23034651