title: CREB phosphorylation coincides with transient synapse formation in the rat hippocampal dentate gyrus following avoidance learning.
abstract: Spine density change in the hippocampal dentate gyrus accompanies memory consolidation and coincides with the increased expression of ribosome-rich, hyperchromatic granule cells. Although this suggests increased protein synthesis to be required for synaptic growth in the 5 to 7 h post-training period, little temporal mapping of the associated molecular mechanisms has been done. Here, we demonstrate a similar frequency of hyperchromatic cells in naïve animals and in those sacrificed 6 h post-training, suggesting a transient repression of protein synthesis in the early post-training period. Immunoblot analysis of CREB phosphorylation in the dentate gyrus supported this view, with downregulation from basal levels observed at 2 to 3 h and at 12 h post-training. Protein synthesis reactivation appears to be specific for de novo spine production as no change in spine frequency accompanies the immediate post-training period of depressed protein synthesis. These findings support the view that CREB-mediated gene transcription is a requirement for long-term memory consolidation and may be directly implicated in the process of synaptic growth.
authors.affiliation: Department of Pharmacology, Conway Institute, University College, Belfield, Dublin 4, Ireland.
authors.forename: C
authors.initials: C
authors.lastname: O'Connell
authors.forename: H C
authors.initials: HC
authors.lastname: Gallagher
authors.forename: A
authors.initials: A
authors.lastname: O'Malley
authors.forename: M
authors.initials: M
authors.lastname: Bourke
authors.forename: C M
authors.initials: CM
authors.lastname: Regan
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D018891:Dentate Gyrus / Q000166:cytology / Q000502:physiology*; D007700:Kinetics; D008297:Male; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D013997:Time Factors
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D010750:Phosphoproteins