Differential expression of long-term potentiation among identified inhibitory inputs to dopamine neurons

J Neurophysiol. 2017 Oct 1;118(4):1998-2008. doi: 10.1152/jn.00270.2017. Epub 2017 Jul 12.


The in vivo firing pattern of ventral tegmental area (VTA) dopamine neurons is controlled by GABA afferents originating primarily from the nucleus accumbens (NAc), rostromedial tegmental nucleus (RMTg), and local GABA neurons within the VTA. Although different forms of plasticity have been observed from GABA inputs to VTA dopamine neurons, one dependent on cyclic GMP synthesis and the other on adenylyl cyclase activation, it is unknown whether plasticity is differentially expressed in each. Using an optogenetic strategy, we show that identified inhibitory postsynaptic currents (IPSCs) from local VTA GABA neurons and NAc afferents exhibit a cyclic GMP-dependent long-term potentiation (LTP) that is capable of inhibiting the firing activity of dopamine neurons. However, this form of LTP was not induced from RMTg afferents. Only an adenylyl cyclase-mediated increase in IPSCs was exhibited by all three inputs. Thus discrete plasticity mechanisms recruit overlapping but different subsets of GABA inputs to VTA dopamine neurons.NEW & NOTEWORTHY We describe a mapping of plasticity expression, mediated by different mechanisms, among three distinct GABA afferents to ventral tegmental area (VTA) dopamine neurons: the rostromedial tegmental nucleus, the nucleus accumbens, and the local GABA neurons within the VTA known to synapse on VTA dopamine neurons. This work is the first demonstration that discrete plasticity mechanisms recruit overlapping but different subsets of GABA inputs to VTA dopamine neurons.

Keywords: GABA inhibition; dopamine neuron; long-term potentiation; nucleus accumbens; rostromedial tegmental nucleus; ventral tegmental area.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cyclic GMP / metabolism
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / physiology*
  • Female
  • GABAergic Neurons / metabolism
  • GABAergic Neurons / physiology
  • Inhibitory Postsynaptic Potentials*
  • Long-Term Potentiation*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nucleus Accumbens / cytology
  • Nucleus Accumbens / physiology
  • Ventral Tegmental Area / cytology
  • Ventral Tegmental Area / physiology


  • Cyclic GMP