Glutamate mediates an inhibitory postsynaptic potential in dopamine neurons

C. D. Fiorillo, John Williams

Research output: Contribution to journalArticle

224 Citations (Scopus)

Abstract

Rapid information transfer within the brain depends on chemical signalling between neurons that is mediated primarily by glutamate and GABA (γ-aminobutyric acid), acting at ionotropic receptors to cause excitatory or inhibitory postsynaptic potentials (EPSPs or IPSPs), respectively. In addition, synaptically released glutamate acts on metabotropic receptors to excite neurons on a slower timescale through second-messenger cascades, including phosphoinositide hydrolysis. We now report a unique IPSP mediated by the activation of metabotropic glutamate receptors. In ventral midbrain dopamine neurons, activation of metabotropic glutamate receptors (mGluR1) mobilized calcium from caffeine/ryanodine-sensitive stores and increased an apaminsensitive potassium conductance. The underlying potassium conductance and dependence on calcium stores set this IPSP apart from the slow IPSPs described so far. The mGluR-induced hyperpolarization was dependent on brief exposure to agonist, because prolonged application of exogenous agonist desensitized the hyperpolarization and caused the more commonly reported depolarization. The rapid rise and brief duration of synaptically released glutamate in the extracellular space can therefore mediate a rapid excitation through activation of ionotropic receptors, followed by inhibition through the mGluR1 receptor. Thus the idea that glutamate is solely an excitatory neurotransmitter must be replaced with a more complex view of its dual function in synaptic transmission.

Original languageEnglish (US)
Pages (from-to)78-82
Number of pages5
JournalNature
Volume394
Issue number6688
DOIs
StatePublished - Jul 2 1998

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Inhibitory Postsynaptic Potentials
Dopaminergic Neurons
Glutamic Acid
Metabotropic Glutamate Receptors
Excitatory Postsynaptic Potentials
Potassium
Calcium
Aminobutyrates
Neurons
Ryanodine
Extracellular Space
Second Messenger Systems
Mesencephalon
Phosphatidylinositols
Caffeine
Synaptic Transmission
gamma-Aminobutyric Acid
Neurotransmitter Agents
Hydrolysis
Brain

ASJC Scopus subject areas

  • General

Cite this

Glutamate mediates an inhibitory postsynaptic potential in dopamine neurons. / Fiorillo, C. D.; Williams, John.

In: Nature, Vol. 394, No. 6688, 02.07.1998, p. 78-82.

Research output: Contribution to journalArticle

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