title: Interaction between N-ethylmaleimide-sensitive factor and GluR2 is essential for fear memory formation in lateral amygdala.
abstract: Long-term memory formation is believed to involve alterations of synaptic efficacy. It has been shown that GluR1-containing AMPA receptors are inserted into synapses following stimuli leading to plasticity and that GluR2/GluR3-containing receptors replace existing synaptic AMPA receptors continuously and may act to maintain synaptic efficacy. Maintaining GluR2/GluR3 receptors level in synapse requires interactions of N-ethylmaleimide-sensitive factor (NSF) with GluR2. To assess possible roles of NSF-GluR2 interaction in rat lateral amygdala (LA) in fear memory formation we used a specific GluR2-NSF interaction inhibitory peptide (pep-R845A). This inhibitory peptide, composed of a modified NSF binding site of GluR2, was previously shown to interact specifically with NSF and to affect AMPA-mediated synaptic efficacy. The inhibitory peptide was linked to a TAT peptide (TAT-pep-R845A) to facilitate internalization into LA cells. Infusion of the TAT-pep-R845A inhibitory peptide into LA 30 min before fear conditioning led to a significant impairment of long-term fear memory formation. In contrast, the control TAT peptide alone had no effect on fear memory. Injection of TAT-pep-R845A peptide into LA had no effect on short-term fear memory. In addition, the inhibitory peptide had no effect on memory retrieval when injected into LA 30 min before fear memory test. Furthermore, maintenance of memory was not impaired when the peptide was injected 24 h after fear conditioning and fear memory was tested 48 h afterward. These results show that GluR2-NSF interaction in LA is necessary for fear memory consolidation but not retrieval or persistence.
authors.affiliation: Department of Neurobiology and Ethology and Biology, University of Haifa, Haifa, Israel.
authors.forename: Gil
authors.initials: G
authors.lastname: Joels
authors.forename: Raphael
authors.initials: R
authors.lastname: Lamprecht
mesh_terms: D000595:Amino Acid Sequence; D000679:Amygdala / Q000502:physiology*; D000818:Animals; D005033:Ethylmaleimide / Q000378:metabolism; D005239:Fear / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D008969:Molecular Sequence Data; D052066:N-Ethylmaleimide-Sensitive Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*
chemical_list: D018091:Receptors, AMPA; D052066:N-Ethylmaleimide-Sensitive Proteins; D005033:Ethylmaleimide; C104722:glutamate receptor ionotropic, AMPA 2