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Homer 1a gates the induction mechanism for endocannabinoid-mediated synaptic plasticity

Academic Article
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Overview

authors

  • Roloff, A. M.
  • Anderson, G. R.
  • Martemyanov, Kirill
  • Thayer, S. A.

publication date

  • February 2010

journal

  • Journal of Neuroscience  Journal

abstract

  • At hippocampal excitatory synapses, endocannabinoids (eCBs) mediate two forms of retrograde synaptic inhibition that are induced by postsynaptic depolarization or activation of metabotropic glutamate receptors (mGluRs). The homer family of molecular scaffolds provides spatial organization to regulate postsynaptic signaling cascades, including those activated by mGluRs. Expression of the homer 1a (H1a) immediate-early gene produces a short homer protein that lacks the domain required for homer oligomerization, enabling it to uncouple homer assemblies. Here, we report that H1a differentially modulates two forms of eCB-mediated synaptic plasticity, depolarization-induced suppression of excitation (DSE) and metabotropic suppression of excitation (MSE). EPSCs were recorded from cultured hippocampal neurons and DSE evoked by a 15 s depolarization to 0 mV and MSE evoked by a type I mGluR agonist. Expression of H1a enhanced DSE and inhibited MSE at the same synapse. Many physiologically important stimuli initiate H1a expression including brain-derived neurotrophic factor (BDNF). Treating hippocampal cultures with BDNF increased transcription of H1a and uncoupled homer 1c-GFP (green fluorescent protein) clusters. BDNF treatment blocked MSE and enhanced DSE. Thus, physiological changes in H1a expression gate the induction pathway for eCB-mediated synaptic plasticity by uncoupling mGluR from eCB production.

subject areas

  • Action Potentials
  • Animals
  • Brain-Derived Neurotrophic Factor
  • Cannabinoid Receptor Modulators
  • Carrier Proteins
  • Cells, Cultured
  • Endocannabinoids
  • Excitatory Amino Acid Agonists
  • Excitatory Postsynaptic Potentials
  • Green Fluorescent Proteins
  • Hippocampus
  • Ion Channel Gating
  • Membrane Potentials
  • Neural Inhibition
  • Neural Pathways
  • Neuronal Plasticity
  • Neurons
  • Rats
  • Receptors, Metabotropic Glutamate
  • Recombinant Fusion Proteins
  • Synapses
  • Synaptic Transmission
  • Transcriptional Activation
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Identity

PubMed Central ID

  • PMC2843151

International Standard Serial Number (ISSN)

  • 0270-6474

Digital Object Identifier (DOI)

  • 10.1523/jneurosci.4603-09.2010

PubMed ID

  • 20181604
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Additional Document Info

start page

  • 3072

end page

  • 3081

volume

  • 30

issue

  • 8

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