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