Postsynaptic mGluR5 promotes evoked AMPAR-mediated synaptic transmission onto neocortical layer 2/3 pyramidal neurons during development

Kristofer W. Loerwald, Ankur B. Patel, Kimberly M. Huber, Jay R. Gibson

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Both short- and long-term roles for the group I metabotropic glutamate receptor number 5 (mGluR5) have been examined for the regulation of cortical glutamatergic synapses. However, how mGluR5 sculpts neocortical networks during development still remains unclear. Using a single cell deletion strategy, we examined how mGluR5 regulates glutamatergic synaptic pathways in neocortical layer 2/3 (L2/3) during development. Electrophysiological measurements were made in acutely prepared slices to obtain a functional understanding of the effects stemming from loss of mGluR5 in vivo. Loss of postsynaptic mGluR5 results in an increase in the frequency of action potential-independent synaptic events but, paradoxically, results in a decrease in evoked transmission in two separate synaptic pathways providing input to the same pyramidal neurons. Synaptic transmission through _-amino-3-hydroxy- 5-methyl-4-isoxazolepropionic acid (AMPA) receptors, but not N-methyl-D-aspartate (NMDA) receptors, is specifically decreased. In the local L2/3 pathway, the decrease in evoked transmission appears to be largely due to a decrease in cell-to-cell connectivity and not in the strength of individual cell-to-cell connections. This decrease in evoked transmission correlates with a decrease in the total dendritic length in a region of the dendritic arbor that likely receives substantial input from these two pathways, thereby suggesting a morphological correlate to functional alterations. These changes are accompanied by an increase in intrinsic membrane excitability. Our data indicate that total mGluR5 function, incorporating both short- and long-term processes, promotes the strengthening of AMPA receptor-mediated transmission in multiple neocortical pathways.

Original languageEnglish (US)
Pages (from-to)786-795
Number of pages10
JournalJournal of neurophysiology
Volume113
Issue number3
DOIs
StatePublished - 2015

Keywords

  • Cortex
  • Metabotropic glutamate receptor
  • Synapse

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

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