A role in learning for SRF: deletion in the adult forebrain disrupts LTD and the formation of an immediate memory of a novel context

Neuron. 2006 Apr 6;50(1):127-43. doi: 10.1016/j.neuron.2006.03.013.


Whereas significant insight exists as to how LTP-related changes can contribute to the formation of long-term memory, little is known about the role of hippocampal LTD-like changes in learning and memory storage. We describe a mouse lacking the transcription factor SRF in the adult forebrain. This mouse could not acquire a hippocampus-based immediate memory for a novel context even across a few minute timespan, which led to a profound but selective deficit in explicit spatial memory. These animals were also impaired in the induction of LTD, including LTD triggered by a cholinergic agonist. Moreover, genes regulating two processes essential for LTD-calcium release from intracellular stores and phosphatase activation-were abnormally expressed in knockouts. These findings suggest that for the hippocampus to form associative spatial memories through LTP-like processes, it must first undergo learning of the context per se through exploration and the learning of familiarity, which requires LTD-like processes.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Behavior, Animal
  • Blotting, Northern / methods
  • Carbachol / pharmacology
  • Cholinergic Agonists / pharmacology
  • Clathrin Heavy Chains / metabolism
  • Discrimination, Psychological / physiology
  • Dose-Response Relationship, Radiation
  • Early Growth Response Protein 1 / metabolism
  • Electric Stimulation / methods
  • Enzyme Inhibitors / pharmacology
  • Exploratory Behavior / physiology*
  • Gene Expression / genetics
  • Gene Expression Regulation, Developmental / physiology
  • Habituation, Psychophysiologic / physiology
  • Hippocampus / metabolism
  • Immunohistochemistry / methods
  • In Situ Hybridization / methods
  • Indoles / pharmacology
  • Learning / physiology*
  • Long-Term Synaptic Depression / genetics
  • Long-Term Synaptic Depression / physiology*
  • Maze Learning / physiology
  • Memory, Short-Term / physiology*
  • Mice
  • Mice, Knockout
  • Models, Neurological
  • Olfactory Bulb / physiology
  • Prosencephalon / physiology*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Serum Response Factor / deficiency
  • Serum Response Factor / physiology*
  • Time Factors


  • Cholinergic Agonists
  • Early Growth Response Protein 1
  • Egr1 protein, mouse
  • Enzyme Inhibitors
  • Indoles
  • RNA, Messenger
  • Serum Response Factor
  • Clathrin Heavy Chains
  • Carbachol
  • cyclopiazonic acid