The ability to learn, form lasting memories, and use stored information to guide future behavior are fundamental and conserved neurobiological processes.
However, the nature and efficacy of these processes are not static across the lifespan of an organism. Many cognitive functions, including learning and memory, mature during adolescence and also show age-related decline.
The importance of successful age-related transitions in neuronal function is highlighted by psychiatric and neurological disorders, including schizophrenia, bipolar disorder, and Alzheimer’s disease, which develop during these transition periods and may represent exaggerated or aberrant maturation processes.
AMPAR Trafficking and Memory
Many studies have implicated synaptic plasticity as a cellular mechanism of learning and memory. Regulated trafficking of AMPA-type glutamate receptors has emerged as a key effector mechanism for expression of synaptic plasticity.
We have found an intriguing age-related requirement for two proteins, PICK1 and KIBRA, which function in a complex to regulate AMPAR trafficking, synaptic plasticity, and learning or memory. Mice lacking either PICK1 or KIBRA show adult onset impairment in hippocampal synaptic plasticity, in spite of missing these proteins throughout development.
Interestingly, alterations in PICK1 function or expression have been linked to schizophrenia, a neuropsychiatric disorder that typically emerges in adolescence or adulthood; KIBRA polymorphisms have been linked to the risk for late-onset Alzheimer’s disease.
We are using these two independent lines of mice to investigate the molecular bases of age-related changes in synapse function, learning, and memory.