A role in learning for SRF: deletion in the adult forebrain disrupts LTD and the formation of an immediate memory of a novel context.
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.
Etkin
Amit
A
Center for Neurobiology and Behavior, Columbia University Medical Center, 1051 Riverside Drive, New York, New York 10032, USA.
Alarcón
Juan Marcos
JM
Weisberg
Stuart P
SP
Touzani
Khalid
K
Huang
Yan You
YY
Nordheim
Alfred
A
Kandel
Eric R
ER
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D015152:Blotting, Northern / Q000379:methods; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D033922:Clathrin Heavy Chains / Q000378:metabolism; D004192:Discrimination, Psychological / Q000502:physiology; D004307:Dose-Response Relationship, Radiation; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005106:Exploratory Behavior / Q000502:physiology*; D015870:Gene Expression / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006185:Habituation, Psychophysiologic / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007211:Indoles / Q000494:pharmacology; D007858:Learning / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000235:genetics / Q000502:physiology*; D018782:Maze Learning / Q000502:physiology; D008570:Memory, Short-Term / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008959:Models, Neurological; D009830:Olfactory Bulb / Q000502:physiology; D016548:Prosencephalon / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D026362:Serum Response Factor / Q000172:deficiency / Q000502:physiology*; D013997:Time Factors
D018679:Cholinergic Agonists; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D004791:Enzyme Inhibitors; D007211:Indoles; D012333:RNA, Messenger; D026362:Serum Response Factor; D033922:Clathrin Heavy Chains; D002217:Carbachol; C000543:cyclopiazonic acid