VTA Projection Neurons Releasing GABA and Glutamate in the Dentate Gyrus

eNeuro. 2016 Sep 13;3(4):ENEURO.0137-16.2016. doi: 10.1523/ENEURO.0137-16.2016. eCollection 2016 Jul-Aug.

Abstract

Both dopamine and nondopamine neurons from the ventral tegmental area (VTA) project to a variety of brain regions. Here we examine nondopaminergic neurons in the mouse VTA that send long-range projections to the hippocampus. Using a combination of retrograde tracers, optogenetic tools, and electrophysiological recordings, we show that VTA GABAergic axons make synaptic contacts in the granule cell layer of the dentate gyrus, where we can elicit small postsynaptic currents. Surprisingly, the currents displayed a partial sensitivity to both bicuculline and NBQX, suggesting that these mesohippocampal neurons corelease both GABA and glutamate. Finally, we show that this projection is functional in vivo and its stimulation reduces granule cell-firing rates under anesthesia. Altogether, the present results describe a novel connection between GABA and glutamate coreleasing of cells of the VTA and the dentate gyrus. This connection could be relevant for a variety of functions, including reward-related memory and neurogenesis.

Keywords: GABA; VTA; corelease; dentate gyrus; glutamate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Animals
  • Dentate Gyrus / cytology
  • Dentate Gyrus / metabolism*
  • Female
  • Glutamate Decarboxylase / metabolism
  • Glutamic Acid / metabolism*
  • Male
  • Mice, Transgenic
  • Neural Pathways / cytology
  • Neural Pathways / metabolism
  • Neuroanatomical Tract-Tracing Techniques
  • Neurons / cytology
  • Neurons / metabolism*
  • Optogenetics
  • Patch-Clamp Techniques
  • Tissue Culture Techniques
  • Ventral Tegmental Area / cytology
  • Ventral Tegmental Area / metabolism*
  • Vesicular Glutamate Transport Protein 2 / metabolism
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Slc17a6 protein, mouse
  • Vesicular Glutamate Transport Protein 2
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2