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.