title: Expression of long-term depression underlies visual recognition memory.
abstract: The modifications occurring in the brain during learning and memory are still poorly understood but may involve long-lasting changes in synaptic transmission (synaptic plasticity). In perirhinal cortex, a lasting decrement in neuronal responsiveness is associated with visual familiarity discrimination, leading to the hypothesis that long-term depression (LTD)-like synaptic plasticity may underlie recognition memory. LTD relies on internalization of AMPA receptors (AMPARs) through interaction between their GluR2 subunits and AP2, the clathrin adaptor protein required for endocytosis. We demonstrate that a peptide that blocks interactions between GluR2 and AP2 blocks LTD in perirhinal cortex in vitro. Viral transduction of this peptide in perirhinal cortex produced striking deficits in visual recognition memory. Furthermore, there was a deficit of LTD in perirhinal cortex slices from virally transduced, recognition memory-deficient animals. These results suggest that internalization of AMPA receptors, a process critical for the expression of LTD in perirhinal cortex, underlies visual recognition memory.
authors.affiliation: MRC Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Griffiths
authors.forename: Helen
authors.initials: H
authors.lastname: Scott
authors.forename: Colin
authors.initials: C
authors.lastname: Glover
authors.forename: Alison
authors.initials: A
authors.lastname: Bienemann
authors.forename: Mohamed T
authors.initials: MT
authors.lastname: Ghorbel
authors.forename: James
authors.initials: J
authors.lastname: Uney
authors.forename: Malcolm W
authors.initials: MW
authors.lastname: Brown
authors.forename: E Clea
authors.initials: EC
authors.lastname: Warburton
authors.forename: Zafar I
authors.initials: ZI
authors.lastname: Bashir
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D033962:Adaptor Protein Complex 2 / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation; D004705:Endocytosis; D018728:Entorhinal Cortex / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005106:Exploratory Behavior; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D018408:Patch-Clamp Techniques / Q000379:methods; D010364:Pattern Recognition, Visual / Q000502:physiology*; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D010775:Photic Stimulation / Q000379:methods; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: D033962:Adaptor Protein Complex 2; D018691:Excitatory Amino Acid Antagonists; D010455:Peptides; D018091:Receptors, AMPA; D049452:Green Fluorescent Proteins; D015763:2-Amino-5-phosphonovalerate; C104722:glutamate receptor ionotropic, AMPA 2