Opioid-sensitive GABA inputs from rostromedial tegmental nucleus synapse onto midbrain dopamine neurons

Aya Matsui, John Williams

Research output: Contribution to journalArticle

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Abstract

Opioids increase dopamine release in the brain through inhibition of GABA-A IPSCs onto dopamine cells. Immunolabeling indicates that GABA neurons in the rostromedial tegmental nucleus (RMTg), also known as the tail of the ventral tegmental area, send a dense projection to midbrain dopamine neurons stain for μ-opioid receptors. There is however, little functional evidence that these neurons play a role in the opioid-dependent increase in dopamine neuron activity. The present study used retrograde tracers injected into the ventral tegmental area and substantia nigra (VTA/SN) to identify RMTg neurons that project to the VTA/SN. Whole-cell current-clamp and cell-attached recordings from labeled RMTg neurons were performed in sagittal slices from rat. The rhythmic spontaneous firing rate of RMTg neurons was decreased and the membrane potential was hyperpolarized in response to application of μ-opioid agonist DAMGO. Agonists that act at κ-and Δ -opioid receptors (U69593 and DPDPE) failed to hyperpolarize RMTg neurons. Whole-cell recordings made in dopamine neurons revealed rhythmic, large amplitude spontaneous IPSCs that had a similar frequency, pattern and opioid sensitivity to the firing of RMTg neurons. In addition, electrical and channelrhodopsin-2 stimulation within the RMTg evoked GABA-A IPSCs in dopamine neurons that were inhibited by μ -opioid agonists DAMGO, but not κ - and Δ -opioid agonists. Thus, this study demonstrates functional connection from the RMTg to the VTA/SN mediated by a dense, opioid-sensitive GABA innervation, and that the RMTg is a key structure in the μ -opioid receptor-dependent regulation of dopamine neurons.

Original languageEnglish (US)
Pages (from-to)17729-17735
Number of pages7
JournalJournal of Neuroscience
Volume31
Issue number48
DOIs
StatePublished - Nov 30 2011

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Dopaminergic Neurons
Mesencephalon
Synapses
gamma-Aminobutyric Acid
Opioid Analgesics
Ventral Tegmental Area
Neurons
Opioid Receptors
Substantia Nigra
Ala(2)-MePhe(4)-Gly(5)-enkephalin
Dopamine
D-Penicillamine (2,5)-Enkephalin
GABAergic Neurons
Patch-Clamp Techniques
Membrane Potentials
Tail
Coloring Agents
Brain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Opioid-sensitive GABA inputs from rostromedial tegmental nucleus synapse onto midbrain dopamine neurons. / Matsui, Aya; Williams, John.

In: Journal of Neuroscience, Vol. 31, No. 48, 30.11.2011, p. 17729-17735.

Research output: Contribution to journalArticle

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