cAMP responsive element-binding protein phosphorylation is necessary for perirhinal long-term potentiation and recognition memory.
We established the importance of phosphorylation of cAMP responsive element-binding protein (CREB) to both the familiarity discrimination component of long-term recognition memory and plasticity within the perirhinal cortex of the temporal lobe. Adenoviral transduction of perirhinal cortex (and adjacent visual association cortex) with a dominant-negative inhibitor of CREB impaired the preferential exploration of novel over familiar objects at a long (24 h) but not a short (15 min) delay, disrupted the normal reduced activation of perirhinal neurons to familiar compared with novel pictures, and impaired long-term potentiation of synaptic transmission in perirhinal slices. The consistency of these effects across the behavioral, systems, and cellular levels of analysis provides strong evidence for involvement of CREB phosphorylation in synaptic plastic processes within perirhinal cortex necessary for long-term recognition memory.
Medical Research Council Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, Bristol BS8 1 TD, United Kingdom.
E Clea
EC
Warburton
Colin P J
CP
Glover
Peter V
PV
Massey
Humin
H
Wan
Ben
B
Johnson
Alison
A
Bienemann
Ule
U
Deuschle
James N C
JN
Kew
John P
JP
Aggleton
Zafar I
ZI
Bashir
James
J
Uney
Malcolm W
MW
Brown
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001245:Association Learning; D000242:Cyclic AMP / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D003673:Defective Viruses / Q000235:genetics; D004193:Discrimination Learning / Q000502:physiology; D004192:Discrimination, Psychological / Q000502:physiology; D018728:Entorhinal Cortex / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials; D005106:Exploratory Behavior / Q000502:physiology*; D017930:Genes, Reporter; D016762:Genes, fos; D005822:Genetic Vectors / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D010364:Pattern Recognition, Visual / Q000502:physiology*; D010766:Phosphorylation; D010775:Photic Stimulation; D011499:Protein Processing, Post-Translational; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics; D016037:Single-Blind Method; D009435:Synaptic Transmission / Q000502:physiology; D013702:Temporal Lobe / Q000502:physiology*; D014158:Transcription, Genetic; D014161:Transduction, Genetic
C508138:A-CREB protein; C508137:Creb1 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D016760:Proto-Oncogene Proteins c-fos; D011993:Recombinant Fusion Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D000242:Cyclic AMP