Genetic enhancement of learning and memory in mice.
Hebb's rule (1949) states that learning and memory are based on modifications of synaptic strength among neurons that are simultaneously active. This implies that enhanced synaptic coincidence detection would lead to better learning and memory. If the NMDA (N-methyl-D-aspartate) receptor, a synaptic coincidence detector, acts as a graded switch for memory formation, enhanced signal detection by NMDA receptors should enhance learning and memory. Here we show that overexpression of NMDA receptor 2B (NR2B) in the forebrains of transgenic mice leads to enhanced activation of NMDA receptors, facilitating synaptic potentiation in response to stimulation at 10-100 Hz. These mice exhibit superior ability in learning and memory in various behavioural tasks, showing that NR2B is critical in gating the age-dependent threshold for plasticity and memory formation. NMDA-receptor-dependent modifications of synaptic efficacy, therefore, represent a unifying mechanism for associative learning and memory. Our results suggest that genetic enhancement of mental and cognitive attributes such as intelligence and memory in mammals is feasible.
Tang
Y P
YP
Department of Molecular Biology, Princeton University, New Jersey 08544-1014, USA.
Shimizu
E
E
Dube
G R
GR
Rampon
C
C
Kerchner
G A
GA
Zhuo
M
M
Liu
G
G
Tsien
J Z
JZ
D000818:Animals; D001245:Association Learning / Q000502:physiology; D002478:Cells, Cultured; D003214:Conditioning, Classical; D003463:Cues; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials; D005239:Fear / Q000502:physiology; D018698:Glutamic Acid / Q000502:physiology; D006624:Hippocampus / Q000502:physiology; D066298:In Vitro Techniques; D007858:Learning; D017774:Long-Term Potentiation; D018782:Maze Learning / Q000502:physiology; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity; D016548:Prosencephalon / Q000502:physiology; D018091:Receptors, AMPA / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D014796:Visual Perception / Q000502:physiology
C121001:NR2B NMDA receptor; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid