Abstract

Memory consolidation in humans and other species is profoundly disrupted by lesions of either the medial temporal lobes or regions of the thalamus. It has been proposed that these structures regulate the neuronal gene expression necessary for long-term memory. Evidence suggests that long-term memory formation requires the activity of members of the cAMP response element (CRE) binding protein (CREB) transcription factor family, and that CRE-regulated genes are expressed in the hippocampus in response to inhibitory avoidance training. Here we show that lesions of the fornix, a massive fiber bundle connecting the hippocampus with the septum and hypothalamus, specifically disrupt both consolidation of inhibitory avoidance memory and CREB-mediated responses in the hippocampus. We propose that inputs passing through the fornix regulate this memory consolidation by regulating CREB-mediated gene expression in hippocampal neurons.