GABAB Receptors Modulate NMDA Receptor Calcium Signals in Dendritic Spines

Jason R. Chalifoux, Adam G. Carter

Research output: Contribution to journalArticle

Abstract

Metabotropic GABAB receptors play a fundamental role in modulating the excitability of neurons and circuits throughout the brain. These receptors influence synaptic transmission by inhibiting presynaptic release or activating postsynaptic potassium channels. However, their ability to directly influence different types of postsynaptic glutamate receptors remains unresolved. Here we examine GABAB receptor modulation in layer 2/3 pyramidal neurons from the mouse prefrontal cortex. We use two-photon laser-scanning microscopy to study synaptic modulation at individual dendritic spines. Using two-photon optical quantal analysis, we first demonstrate robust presynaptic modulation of multivesicular release at single synapses. Using two-photon glutamate uncaging, we then reveal that GABAB receptors strongly inhibit NMDA receptor calcium signals. This postsynaptic modulation occurs via the PKA pathway and does not affect synaptic currents mediated by AMPA or NMDA receptors. This form of GABAB receptor modulation has widespread implications for the control of calcium-dependent neuronal function.

Original languageEnglish (US)
Pages (from-to)101-113
Number of pages13
JournalNeuron
Volume66
Issue number1
DOIs
StatePublished - Apr 1 2010

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Keywords

  • Molneuro
  • Signaling

ASJC Scopus subject areas

  • Neuroscience(all)

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