Endogenous GluR1-containing AMPA receptors translocate to asymmetric synapses in the lateral amygdala during the early phase of fear memory formation

An electron microscopic immunocytochemical study

Hermina Nedelescu, Catherine M. Kelso, Gabriel Lázaro-Muñoz, Mari Purpura, Christopher K. Cain, Joseph Ledoux, Chiye Aoki

Research output: Contribution to journalArticle

Abstract

Although glutamate receptor 1 (GluR1)-containing α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (GluR1-AMPARs) are implicated in synaptic plasticity, it has yet to be demonstrated whether endogenous GluR1-AMPARs undergo activity-dependent trafficking in vivo to synapses to support short-term memory (STM) formation. The paradigm of pavlovian fear conditioning (FC) can be used to address this question, because a discrete region-the lateral amygdala (LA)-has been shown unambiguously to be necessary for the formation of the associative memory between a neutral stimulus (tone [CS]) and a noxious stimulus (foot shock [US]). Acquisition of STM for FC can occur even in the presence of protein synthesis inhibitors, indicating that redistribution of pre-existing molecules to synaptic junctions underlies STM. We employed electron microscopic immunocytochemistry to evaluate alterations in the distribution of endogenous AMPAR subunits at LA synapses during the STM phase of FC. Rats were sacrificed 40 minutes following three CS-US pairings. In the LA of paired animals, relative to naïve animals, the proportion of GluR1-AMPAR-labeled synapses increased 99% at spines and 167% in shafts. In the LA of unpaired rats, for which the CS was never associated with the US, GluR1 immunoreactivity decreased 84% at excitatory shaft synapses. GluR2/3 immunoreactivity at excitatory synapses did not change detectably following paired or unpaired conditioning. Thus, the early phase of FC involves rapid redistribution specifically of the GluR1-AMPARs to the postsynaptic membranes in the LA, together with the rapid translocation of GluR1-AMPARs from remote sites into the spine head cytoplasm, yielding behavior changes that are specific to stimulus contingencies.

Original languageEnglish (US)
Pages (from-to)4723-4739
Number of pages17
JournalJournal of Comparative Neurology
Volume518
Issue number23
DOIs
StatePublished - Dec 1 2010

Fingerprint

AMPA Receptors
Glutamate Receptors
Amygdala
Synapses
Fear
Electrons
Short-Term Memory
Spine
Isoxazoles
Neuronal Plasticity
Protein Synthesis Inhibitors
Propionates
Hydroxyl Radical
Foot
Shock
Cytoplasm
Immunohistochemistry
Conditioning (Psychology)
Membranes

Keywords

  • Associative memory
  • Auditory cue
  • Conditioned inhibition
  • Endogenous gene products
  • Fear conditioning
  • Pavlovian
  • Receptor trafficking
  • Stimulus contingencies
  • STM, LTM
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Endogenous GluR1-containing AMPA receptors translocate to asymmetric synapses in the lateral amygdala during the early phase of fear memory formation : An electron microscopic immunocytochemical study. / Nedelescu, Hermina; Kelso, Catherine M.; Lázaro-Muñoz, Gabriel; Purpura, Mari; Cain, Christopher K.; Ledoux, Joseph; Aoki, Chiye.

In: Journal of Comparative Neurology, Vol. 518, No. 23, 01.12.2010, p. 4723-4739.

Research output: Contribution to journalArticle

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abstract = "Although glutamate receptor 1 (GluR1)-containing α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (GluR1-AMPARs) are implicated in synaptic plasticity, it has yet to be demonstrated whether endogenous GluR1-AMPARs undergo activity-dependent trafficking in vivo to synapses to support short-term memory (STM) formation. The paradigm of pavlovian fear conditioning (FC) can be used to address this question, because a discrete region-the lateral amygdala (LA)-has been shown unambiguously to be necessary for the formation of the associative memory between a neutral stimulus (tone [CS]) and a noxious stimulus (foot shock [US]). Acquisition of STM for FC can occur even in the presence of protein synthesis inhibitors, indicating that redistribution of pre-existing molecules to synaptic junctions underlies STM. We employed electron microscopic immunocytochemistry to evaluate alterations in the distribution of endogenous AMPAR subunits at LA synapses during the STM phase of FC. Rats were sacrificed 40 minutes following three CS-US pairings. In the LA of paired animals, relative to na{\"i}ve animals, the proportion of GluR1-AMPAR-labeled synapses increased 99{\%} at spines and 167{\%} in shafts. In the LA of unpaired rats, for which the CS was never associated with the US, GluR1 immunoreactivity decreased 84{\%} at excitatory shaft synapses. GluR2/3 immunoreactivity at excitatory synapses did not change detectably following paired or unpaired conditioning. Thus, the early phase of FC involves rapid redistribution specifically of the GluR1-AMPARs to the postsynaptic membranes in the LA, together with the rapid translocation of GluR1-AMPARs from remote sites into the spine head cytoplasm, yielding behavior changes that are specific to stimulus contingencies.",
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AU - Lázaro-Muñoz, Gabriel

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