Genetic enhancement of learning and memory in mice

Hebb's rule (1949) states that learning and memory are based on modificatio ns of synaptic strength among neurons that are simultaneously active. This implies that enhanced synaptic coincidence detection would lead to better l earning and memory. If the NMDA (N-methyl-D-aspartate) receptor, a synaptic coincidence detector(1-4), acts as a graded switch for memory formation, e nhanced signal detection by NMDA receptors should enhance learning and memo ry. Here we show that overexpression of NMDA receptor 2B (NR2B) in the fore brains of transgenic mice leads to enhanced activation of NMDA receptors, f acilitating synaptic potentiation in response to stimulation at 10-100 Hz. These mice exhibit superior ability in learning and memory in various behav ioural tasks, showing that NR2B is critical in gating the age-dependent thr eshold for plasticity and memory formation. NMDA-receptor-dependent modific ations of synaptic efficacy, therefore, represent a unifying mechanism for associative learning and memory. Our results suggest that genetic enhanceme nt of mental and cognitive attributes such as intelligence and memory in ma mmals is feasible.