Impaired Hippocampal Representation of Space in CA1-Specific NMDAR1 Knockout Mice

@article{McHugh1996ImpairedHR,
  title={Impaired Hippocampal Representation of Space in CA1-Specific NMDAR1 Knockout Mice},
  author={Thomas J. McHugh and K. I. Blum and Joe Z. Tsien and Susumu Tonegawa and Matthew A. Wilson},
  journal={Cell},
  year={1996},
  volume={87},
  pages={1339-1349}
}
To investigate the role of synaptic plasticity in the place-specific firing of the hippocampus, we have applied multiple electrode recording techniques to freely behaving mice with a CA1 pyramidal cell-specific knockout of the NMDAR1 gene. We have discovered that although the CA1 pyramidal cells of these mice retain place-related activity, there is a significant decrease in the spatial specificity of individual place fields. We have also found a striking deficit in the coordinated firing of… Expand

Paper Mentions

The Essential Role of Hippocampal CA1 NMDA Receptor–Dependent Synaptic Plasticity in Spatial Memory
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The results strongly suggest that activity-dependent modifications of CA1 synapses, mediated by NMDA receptors, play an essential role in the acquisition of spatial memories. Expand
Differential contribution of NMDA receptors in hippocampal subregions to spatial working memory
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Dentate Gyrus NMDA Receptors Mediate Rapid Pattern Separation in the Hippocampal Network
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Behavioral deficits and subregion-specific suppression of LTP in mice expressing a population of mutant NMDA receptors throughout the hippocampus.
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The data show that minor changes in GluN1-dependent NMDAR physiology can cause dramatic consequences in synaptic signaling in a subregion-specific fashion despite the nonredundant nature of the Glun1 gene and its global expression. Expand
Hippocampal place cells, spatial memory, and synaptic plasticity
  • 1997
was accompanied by impaired spatial memory (but normal nonspatial learning) in these mutants. They also observed that, while CAl pyramidal cells in these mice exhibit place-related activity, spatialExpand
Formation of Temporal Memory Requires NMDA Receptors within CA1 Pyramidal Neurons
TLDR
This work applied trace fear conditioning to knockout mice lacking NMDARs only in hippocampal CA1 pyramidal cells and found that knockout mice failed to memorize this association but were indistinguishable from normal animals when the trace was removed. Expand
NMDA receptors, place cells and hippocampal spatial memory
TLDR
The data that have emerged from in vivo hippocampal recording studies that indicate that the activity of hippocampal place cells during behaviour is an expression of a memory trace are discussed. Expand
Enrichment induces structural changes and recovery from nonspatial memory deficits in CA1 NMDAR1-knockout mice
TLDR
It is found that enrichment induced an increase of the synapse density in the CA1 region in knockouts as well as control littermates, which indicates that CA1 NMDA receptor activity is critical in hippocampus-dependent nonspatial memory, but is not essential for experience-induced synaptic structural changes. Expand
Abolition of long-term stability of new hippocampal place cell maps by NMDA receptor blockade.
TLDR
The results suggest that the formation and short-term stability of firing fields in a new environment involve plasticity that is independent of NMDA receptor activation, and may be related to other NMDA-dependent processes such as long-term potentiation and spatial learning. Expand
Single-Trial Properties of Place Cells in Control and CA1 NMDA Receptor Subunit 1-KO Mice
TLDR
It is suggested that deficits in place field size and spatial information are rescued by extensive exposure of the mouse to the track, which may echo an increased influence of memory retrieval processes in CA3 on firing in CA1. Expand
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References

SHOWING 1-10 OF 44 REFERENCES
The Essential Role of Hippocampal CA1 NMDA Receptor–Dependent Synaptic Plasticity in Spatial Memory
TLDR
The results strongly suggest that activity-dependent modifications of CA1 synapses, mediated by NMDA receptors, play an essential role in the acquisition of spatial memories. Expand
Place navigation impaired in rats with hippocampal lesions
TLDR
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. Expand
Dynamics of the hippocampal ensemble code for space.
TLDR
Parallel recording methods outlined here make possible the study of the dynamics of neuronal interactions during unique behavioral events, which suggests that new spatial information creates conditions in the hippocampal circuitry that are conducive to the synaptic modification presumed to be involved in learning. Expand
Deficient hippocampal long-term potentiation in alpha-calcium-calmodulin kinase II mutant mice.
TLDR
W Whole cell recordings reveal that postsynaptic mechanisms, including N-methyl-D-aspartate (NMDA) receptor function, are intact and are therefore a suitable model for studying the relation between LTP and learning processes. Expand
Heightened synaptic plasticity of hippocampal CA1 neurons during a Cholinergically induced rhythmic state
TLDR
The results suggest that cholinergic systems may affect memory formation through the induction of an oscillatory state in which the requirements for synaptic plasticity are dramatically altered. Expand
Impaired spatial learning in alpha-calcium-calmodulin kinase II mutant mice.
TLDR
The data considerably strengthen the contention that the synaptic changes exhibited in LTP are the basis for spatial memory. Expand
Experience-dependent modification of synaptic plasticity in visual cortex
TLDR
In visual cortex of light-deprived rats that LTP is enhanced and LTD diminished over a range of stimulation frequencies, and that these effects can be reversed by as little as two days of light exposure, support the idea that a variable synaptic-modification threshold allows synaptic weights in neural networks to achieve a stable equilibrium. Expand
Distinct components of spatial learning revealed by prior training and NMDA receptor blockade
TLDR
It is reported that the AP5-induced learning deficit can be almost completely prevented if rats are pretrained in a different watermaze before administration of the drug. Expand
The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat.
TLDR
Preliminary observations on the behaviour of hippocampusal units in the freely moving rat provide support for this theory of hippocampal function. Expand
Spatial learning without NMDA receptor-dependent long-term potentiation
TLDR
It is reported that NPC17742 completely blocked dentate gyrus LTP but did not prevent normal spatial learning in rats that had been made familiar with the general task requirements by non-spatial pretraining, indicating that this form of LTP is not required for normal spatiallearning in the watermaze. Expand
...
1
2
3
4
5
...