Jessica A. Cardin, Ted Abel

Memory suppressor genes encode proteins that act as inhibitory constraints to impede memory storage. The study of memory suppressor genes is important not only for understanding the link between synaptic plasticity and learning but also for identifying potential targets for future pharmaceuticals to treat memory disorders. This article first reviews the evidence for proteins that impede memory storage from work in invertebrates and then explores recent evidence for the existence of memory suppressor genes in vertebrates in the context of hippocampus-dependent forms of memory. In Aplysia, memory suppressor gene products act at each step in long-term facilitation: in the cytoplasm to regulate kinase activity, in the nucleus to alter the activity of transcriptional regulatory proteins, and on the cell surface to modulate cell-cell interactions. Studies of genetically modified Drosophila have provided behavioral evidence for the existence of memory suppressor genes. One of the best candidates for a neuronal mechanism underlying learning is long-term potentiation (LTP), which has been extensively studied in the mammalian hippocampus. Recent work has identified a number of putative memory suppressor gene products that act in the hippocampus at the levels of LTP induction, regulation of intracellular signaling cascades, and transcriptional control. Using these gene products as tools to study enhancements rather than deficits in LTP and learning may generate more precise information about the relationship between synaptic plasticity and behavioral learning. The study of mammalian memory suppressor genes may provide insights into alleviating the learning and memory deficits that accompany both normal aging and a variety of human disorders.