Bursting of prefrontal cortex neurons in awake rats is regulated by metabotropic glutamate 5 (mGlu5) receptors: Rate-dependent influence and interaction with NMDA receptors

Houman Homayoun, Bita Moghaddam

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Metabotropic glutamate 5 (mGlu5) receptors have been recently implicated in prefrontal cortex (PFC)-dependent executive functions because inhibition of mGlu5 receptors impairs working memory and worsens cognitive-impairing effects of NMDA receptor antagonists. To better understand the mechanisms by which mGlu5 receptors influence PFC function, we examined the effects of selective mGlu5 receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP), given alone or in combination with the NMDA receptor antagonist MK801, on ensemble single unit activity in the medial PFC (mPFC) of behaving rats. MPEP decreased the spontaneous burst activity of the majority of mPFC neurons. This inhibition was selective for the most active cells because greater decreases were observed in neurons with higher baseline firing rates. MPEP augmented the effects of MK801 on burst activity, variability of spike firing and random spike activity. These findings demonstrate that in awake animals mGlu5 receptors regulate the function of PFC neurons by two related mechanisms: (i) rate-dependent excitatory influence on spontaneous burst activity; and (ii) potentiation of NMDA receptor mediated effects on firing rate and burst activity. These mechanisms support the idea that modulation of mGlu5 receptors may provide a pharmacological strategy for fine-tuning the temporal pattern of firing of PFC neurons.

Original languageEnglish (US)
Pages (from-to)93-105
Number of pages13
JournalCerebral Cortex
Volume16
Issue number1
DOIs
StatePublished - Jan 2006
Externally publishedYes

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Metabotropic Glutamate 5 Receptor
Prefrontal Cortex
N-Methyl-D-Aspartate Receptors
Neurons
Excitatory Amino Acid Antagonists
Executive Function
Short-Term Memory
Pharmacology

Keywords

  • Ensemble single unit recording
  • Metabotropic glutamate receptors
  • NMDA receptor hypofunction
  • Prefrontal cortex
  • Schizophrenia

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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abstract = "Metabotropic glutamate 5 (mGlu5) receptors have been recently implicated in prefrontal cortex (PFC)-dependent executive functions because inhibition of mGlu5 receptors impairs working memory and worsens cognitive-impairing effects of NMDA receptor antagonists. To better understand the mechanisms by which mGlu5 receptors influence PFC function, we examined the effects of selective mGlu5 receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP), given alone or in combination with the NMDA receptor antagonist MK801, on ensemble single unit activity in the medial PFC (mPFC) of behaving rats. MPEP decreased the spontaneous burst activity of the majority of mPFC neurons. This inhibition was selective for the most active cells because greater decreases were observed in neurons with higher baseline firing rates. MPEP augmented the effects of MK801 on burst activity, variability of spike firing and random spike activity. These findings demonstrate that in awake animals mGlu5 receptors regulate the function of PFC neurons by two related mechanisms: (i) rate-dependent excitatory influence on spontaneous burst activity; and (ii) potentiation of NMDA receptor mediated effects on firing rate and burst activity. These mechanisms support the idea that modulation of mGlu5 receptors may provide a pharmacological strategy for fine-tuning the temporal pattern of firing of PFC neurons.",
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