Genes for Learning and Memory

An interactive chromosome map of the genes and loci associated with learning and memory.

An interactive chromosome map of the genes and loci associated with learning and memory.

Learning and memory: DLG3:Discs, large homolog 3 (DLG3) is a gene associated with learning and memory. DLG3 encodes synapse-associated protein 102 (SAP102). During early brain development, SAP102 is expressed in neurons in the postsynaptic density of excitatory synapses. It interacts directly with the NMDA receptor complex, which plays an important role in long-term potentiation and memory formation. Tarpey and colleagues (2004) linked mutations in DLG3 with X-linked mental retardation, which prematurely creates a stop codon, causing the protein to terminate too soon. It is likely that this mutation disrupts SAP102 interactions with the NMDA receptor complex. Cuthbert and colleagues (2007) found that mice lacking SAP102 had impaired synaptic plasticity and showed deficits in spatial learning. DLG4: Discs, large homolog 4 (DLG4) is a gene associated with learning and memory. The human DLG4 protein is 99% identical to the rat and mouse Psd95 proteins. Migaud and colleagues (1998) examined mice that lack this protein and found evidence of severe impairments in spatial learning. This was reflected by irregularities in long-term potentiation in the brain. These changes may be caused by a disruption of the NMDA receptor, which can bind Psd95, at the synapse. In the absence of Psd95, the NMDA receptor synaptic may become uncoupled from pathways that control plasticity and learning. CREB1: CAMP response element-binding (CREB) proteins are transcription factors which bind to sequences of DNA called cAMP response elements. When signals arrive at receptors (e.g. glutamate receptors) on a cell's surface, a series of protein-protein interactions lead to the production of cAMP, which in turn activates a protein kinase. This kinase migrates to the cell's nucleus where it activates CREB. Once activated, CREB proteins coordinate a series of interactions that can turn on and off certain genes. CREB proteins in neurons are involved in the formation of long-term memories and are involved in long-term potentiation. CREB1 is a CREB activator, which means it facilitates long-term memory formation. A 1995 paper by Jerry Yin and Tim Tully at Cold Spring Harbor Laboratory examined the CREB1 protein in fruit flies (or rather the fruit-fly homolog dCREB2). Overproduction of the protein led the flies to develop an equivalent of photographic memory. CREB2: CAMP response element-binding (CREB) proteins are transcription factors which bind to sequences of DNA called cAMP response elements. When signals arrive at receptors (e.g. glutamate receptors) on a cell's surface, a series of protein-protein interactions lead to the production of cAMP, which in turn activates a protein kinase. This kinase migrates to the cell's nucleus where it activates CREB. Once activated, CREB proteins coordinate a series of interactions that can turn on and off certain genes. CREB proteins in neurons are involved in the formation of long-term memories and are involved in long-term potentiation. CREB2 is also known as Activating Transcription Factor 2 (ATF2). CREB2 is a CREB repressor, which means it inhibits long-term memory formation. Bartsch, Kandel and colleagues (1995) studied CREB2 in Aplysia (sea slug). When CREB2 repression was relieved, it became easier for the animals to lay down long-term memories.