Ventral Tegmental Area Glutamate Neurons: Electrophysiological Properties and Projections

J Neurosci. 2012 Oct 24;32(43):15076-85. doi: 10.1523/JNEUROSCI.3128-12.2012.

Abstract

The ventral tegmental area (VTA) has a central role in the neural processes that underlie motivation and behavioral reinforcement. Although thought to contain only dopamine and GABA neurons, the VTA also includes a recently discovered population of glutamate neurons identified through the expression of the vesicular glutamate transporter VGLUT2. A subset of VGLUT2(+) VTA neurons corelease dopamine with glutamate at terminals in the NAc, but others do not express dopaminergic markers and remain poorly characterized. Using transgenic mice that express fluorescent proteins in distinct cell populations, we now find that both dopamine and glutamate neurons in the medial VTA exhibit a smaller hyperpolarization-activated current (I(h)) than more lateral dopamine neurons and less consistent inhibition by dopamine D(2) receptor agonists. In addition, VGLUT2(+) VTA neurons project to the nucleus accumbens (NAc), lateral habenula, ventral pallidum (VP), and amygdala. Optical stimulation of VGLUT2(+) projections expressing channelrhodopsin-2 further reveals functional excitatory synapses in the VP as well as the NAc. Thus, glutamate neurons form a physiologically and anatomically distinct subpopulation of VTA projection neurons.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biophysics
  • Channelrhodopsins
  • Dopamine Agonists / pharmacology
  • Dopamine Plasma Membrane Transport Proteins / genetics
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Electric Stimulation
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glutamic Acid / metabolism*
  • In Vitro Techniques
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Membrane Potentials / drug effects
  • Membrane Potentials / genetics
  • Membrane Potentials / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neural Pathways / physiology*
  • Neurons / classification
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Quinoxalines / pharmacology
  • Quinpirole / pharmacology
  • Tyrosine 3-Monooxygenase / metabolism
  • Ventral Tegmental Area / cytology*
  • Vesicular Glutamate Transport Protein 2 / genetics

Substances

  • Channelrhodopsins
  • Dopamine Agonists
  • Dopamine Plasma Membrane Transport Proteins
  • Excitatory Amino Acid Antagonists
  • Luminescent Proteins
  • Quinoxalines
  • Slc17a6 protein, mouse
  • Vesicular Glutamate Transport Protein 2
  • Quinpirole
  • Glutamic Acid
  • FG 9041
  • Tyrosine 3-Monooxygenase