Genetic enhancement of learning and memory in mice

  title={Genetic enhancement of learning and memory in mice},
  author={Ya-ping Tang and Eiji Shimizu and Gilles R. Dub{\'e} and Claire Rampon and Geoffrey A. Kerchner and Min Zhuo and Guosong Liu and Joe Z. Tsien},
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… 

Genetic Enhancement of Memory and Long-Term Potentiation but Not CA1 Long-Term Depression in NR2B Transgenic Rats

The genetic experiments suggest that NR2B at CA1 synapses is not designated as a rate-limiting factor for the induction of long-term synaptic depression, but rather plays a crucial role in initiating the synaptic potentiation.

Enhancement of Learning and Memory by Elevating Brain Magnesium

Plasticity, hippocampal place cells, and cognitive maps.

  • M. Shapiro
  • Biology, Psychology
    Archives of neurology
  • 2001
Hippocampal cells "learn" to encode the salient features of experience through NMDA receptor-dependent synaptic plasticity mechanisms, and this rapid and persistent neuronal encoding is a crucial step toward the formation of long-term memory.

Targeting NR2B for Memory Improvement

The creation of Doogie mice has demonstrated that it is possible to manipulate a single NMDA receptor subunit for a broad range of learning and memory enhancement, and cross-species validation adds to the notion that NR2B may act as a universal key switch for gating memory enhancement in various mammalian brains.

Synaptic plasticity and memory: an evaluation of the hypothesis.

It is concluded that a wealth of data support the notion that synaptic plasticity is necessary for learning and memory, but that little data currently supports the notion of sufficiency.

Maintenance of superior learning and memory function in NR2B transgenic mice during ageing

It is concluded that increased expression of NR2B in the forebrain improves learning and memory function in the aged brain.


It is concluded that the time is too early to judge clearly if LTP is a real mechanism of learning and memory.

Pretraining and the Function of Hippocampal Long-Term Potentiation

Rapid and Transient Learning-Associated Increase in NMDA NR1 Subunit in the Rat Hippocampus

The present findings support the hypothesis that alterations in expression of synaptic NMDA NR1 subunits in the hippocampus are specifically associated with memory formation of an inhibitory avoidance task and strongly suggest that hippocampal NMDA receptors are crucially involved in the neural mechanisms underlying certain forms of learning.



Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein

In mutant mice lacking PSD-95, the frequency function of NMDA-dependent LTP and LTD is shifted to produce strikingly enhanced LTP at different frequencies of synaptic stimulation, which is accompanied by severely impaired spatial learning.

Activity-dependent decrease in NMDA receptor responses during development of the visual cortex.

A modification of the NMDA receptor gating properties may account for the age-dependent decline of visual cortical plasticity.

Synaptic plasticity

Extinction of fear-potentiated startle: blockade by infusion of an NMDA antagonist into the amygdala

The results show that infusion of the NMDA antagonist D,L-2- amino-5-phosphonovaleric acid (AP5) into the amygdala, a limbic structure known to be important for fear conditioning, dose-dependently blocked extinction of conditioned fear and suggest that an NMDA-dependent process might underlie the extinction of Conditioned fear.

A synaptic model of memory: long-term potentiation in the hippocampus

The best understood form of long-term potentiation is induced by the activation of the N-methyl-d-aspartate receptor complex, which allows electrical events at the postsynaptic membrane to be transduced into chemical signals which, in turn, are thought to activate both pre- and post Synaptic mechanisms to generate a persistent increase in synaptic strength.

Hippocampal Synaptic Plasticity in Mice Overexpressing an Embryonic Subunit of the NMDA Receptor

It is shown that the developmental regulation of NMDA receptor subunit composition alters the frequency at which modification of synaptic responses occur after afferent stimulation, which is correlated with a marked impairment ofNMDA-dependent long-term potentiation.

Bidirectional long-term modification of synaptic effectiveness in the adult and immature hippocampus

  • SM DudekMF Bear
  • Biology
    The Journal of neuroscience : the official journal of the Society for Neuroscience
  • 1993
To address the question of whether depressed synapses can still be potentiated and vice versa, LTP was saturated with repeated high- frequency tetani, and then LTD was induced with low-frequency stimulation (LFS), indicating that the same synapses whose transmission had been depressed by LFS were capable of subsequently supporting potentiation.

Place navigation impaired in rats with hippocampal lesions

It is reported that, in addition to a spatial discrimination impairment, total hippocampal lesions also cause a profound and lasting placenavigational impairment that can be dissociated from correlated motor, motivational and reinforcement aspects of the procedure.