Ultrastructural and optogenetic evidence for dual neuronal signaling by dopamine neurons of the ventral tegmental area (VTA)

Thursday, October 11, 2012 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center, Building 45	NIDA	NEURO/BEHAV/SENSYS-28

Authors

• S. Zhang
• X. Li
• H. Wang
• J. Qi
• J.P. Britt
• A. Bonci
• M. Morales

Abstract

Dopamine (DA) neurons expressing tyrosine hydroxylase (TH) play a role in movement, motivation, learning and reward. The ventral tegmental area (VTA) contains a subset of DA neurons that co-express transcripts encoding the vesicular glutamate transporter 2 (VGluT2). The dual DA-VGluT2 neurons target the medial prefrontal cortex (mPFC) and the nucleus accumbens (nAcc), and have the capability to co-release dopamine and glutamate. To investigate whether the dual DA-VGluT2 neurons could mediate synaptic co-release of dopamine and glutamate, we performed in vivo tagging of VTA neurons in rats or transgenetic mice (TH::Cre or VGluT2::Cre mice). Our study showed that TH and VGluT2 do not co-exist in the same axon terminal. By fluorescent and electron microscopy, TH or dopamine transporter (DAT) was observed in the contiguous axons of axon terminals containing VGluT2. By combination of ex vivo electrophysiology and optogenetics, we provide for the first time evidence indicating that a brain involved in addictive behaviors has a unique set of neurons with the unanticipated capability to co-release two different signaling molecules from two distinct subcellular compartments: glutamate from axon terminals, and dopamine mostly from axons. Further studies are necessary to determine the role of this novel dual signaling mechanism in brain function.

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