RESEARCH HIGHLIGHTS

NEUROTRANSMITTERS neurons recycle GABA

Many neurons in the activation of GABA type A (GABAA) into GABA. However, blockade of receptors. Here, the authors showed GABA transaminase did not reduce (SNc) and in ex vivo mouse brain slices that optogenetically evoked IPSCs. These (VTA) signal to striatal projection optogenetic activation of VTA neu- data suggest that dopaminergic SNc neurons (SPNs). Mounting evidence rons evoked inhibitory postsynaptic and VTA neurons do not synthesize indicates that these dopaminergic currents (IPSCs) in SPNs that could GABA for inhibitory transmission.

neurons co-release other neuro- be blocked by picrotoxin, a GABAA Strikingly, many SNc and VTA transmitters, although the details receptor antagonist. Moreover, neurons showed expression of of this co-transmission remain to they found that acute antagonism mGAT1 and mGAT4, and chronic be fully established. In a new study, of the GABA reuptake transporter incubation (>30 minutes) of striatal Sabatini and colleagues show that mGAT1, which is expressed on slices with mGAT1 and mGAT4 dopaminergic midbrain neurons co- GABAergic presynaptic terminals, inhibitors dramatically reduced the release GABA and that, surprisingly, slowed the decay of IPSCs in SPNs amplitude of optogenetically induced the source of this is after optogenetic activation of SNc or IPSCs in SPNs. Thus, the authors extracellular. VTA neurons. Together, these results propose that mGAT1 and mGAT4 In a previous study, the authors indicate that GABA is co-released by transporters enable SNc and VTA found that activation of SNc dopa- midbrain dopamine neurons. neurons to ‘recycle’ extracellular mine neurons inhibits SPNs through The authors next sought to deter- GABA for release. mine the origin of the presynaptic Overall, this study provides mGAT1 GABA using immunohistochemical evidence that GABA is co-released by and mGAT4 and in situ hybridization analyses. SNc and VTA dopaminergic neurons These approaches revealed that and that rather than being synthe- inhibitors hardly any dopaminergic SNc or sized de novo, this GABA is derived dramatically VTA neurons exhibited expression from outside neurons and taken up reduced the of the 65 kDa or 67 kDa isoforms of by mGATs. glutamic acid decarboxylase (GAD Natasha Bray amplitude of 65 or GAD67) — the main enzymes optogenetically responsible for GABA synthesis in the ORIGINAL RESEARCH PAPER Tritsch, N. X. et al. Midbrain dopamine neurons sustain inhibitory induced IPSCs CNS — although these neurons did transmission using plasma membrane uptake of express GABA transaminase, which GABA, not synthesis. eLife http://dx.doi. NPG converts succinate semialdehyde org/10.7554/eLife.01936 (2014)

NATURE REVIEWS | NEUROSCIENCE VOLUME 15 | JUNE 2014

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