Dentate Gyrus NMDA Receptors Mediate Rapid Pattern Separation in the Hippocampal Network

  title={Dentate Gyrus NMDA Receptors Mediate Rapid Pattern Separation in the Hippocampal Network},
  author={Thomas J. McHugh and Matthew W. Jones and JenniferJ . Quinn and Nina Balthasar and Roberto Coppari and Joel K Elmquist and Bradford B. Lowell and Michael S. Fanselow and Matthew A. Wilson and Susumu Tonegawa},
  pages={94 - 99}
Forming distinct representations of multiple contexts, places, and episodes is a crucial function of the hippocampus. The dentate gyrus subregion has been suggested to fulfill this role. We have tested this hypothesis by generating and analyzing a mouse strain that lacks the gene encoding the essential subunit of the N-methyl-d-aspartate (NMDA) receptor NR1, specifically in dentate gyrus granule cells. The mutant mice performed normally in contextual fear conditioning, but were impaired in the… 

Behavioral deficits and subregion-specific suppression of LTP in mice expressing a population of mutant NMDA receptors throughout the hippocampus.

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.

Enhanced stability of hippocampal place representation caused by reduced magnesium block of NMDA receptors in the dentate gyrus

These results suggest that the Mg2+ block in the dentate gyrus regulates hippocampal spatial information processing by attenuating activity-dependent synaptic potentiation in the dentist's gyrus.

Dendritic integration in hippocampal dentate gyrus granule cells

These experiments revealed unusual integrative properties of the small-caliber granule cell dendrites that can enhance contrast in the generation of place-specific firing maps from entorhinal inputs and contribute to the sparse representation of space in the dentate gyrus.

GluN2A-/- Mice Lack Bidirectional Synaptic Plasticity in the Dentate Gyrus and Perform Poorly on Spatial Pattern Separation Tasks.

The results establish the GluN2A subunit as a significant contributor to both bidirectional synaptic plasticity and spatial pattern separation in the DG, a process associated with CA1 functioning.

Pattern Separation in the Human Hippocampal CA3 and Dentate Gyrus

High-resolution functional magnetic resonance imaging is used to measure brain activity during incidental memory encoding and provides compelling evidence of a key role of the human CA3/dentate gyrus in pattern separation.

Role of NMDA Receptors in Adult Neurogenesis and Normal Development of the Dentate Gyrus

The results suggest that the NMDA receptors in granule cells have a role in adult neurogenesis in the adult brain and contributes to the normal development of the dentate gyrus.

Dentate gyrus circuits for encoding, retrieval and discrimination of episodic memories

The cells and circuits of the dentate gyrus are examined, and evidence indicating that this brain region has multiple mnemonic functions is discussed, to explore mechanistic links between the cellular and network properties of, and the computations performed by, the DG.

Perforant path inputs to hippocampal subfields predict heterogeneous AMPA receptor subunit expression following rapid new spatial learning in a novel context

Differences in GluA2:GluA1 expression trends between time points and room conditions that mirror trends in medial and lateral entorhinal cortex connectivity between new room and same room context learning, respectively are identified.

Heterosynaptic NMDA Receptor Plasticity in Hippocampal Dentate Granule Cells

The findings uncover a mechanism by which distinct inputs to the dentate gyrus may interact functionally and contribute to hippocampal-dependent memory formation, and provide the first evidence for heterosynaptic NMDAR plasticity, which may have important consequences on the dendritic integration of functionally distinct excitatory inputs by dentate granule cells.



Requirement for Hippocampal CA3 NMDA Receptors in Associative Memory Recall

Results provide direct evidence for CA3 NMDA receptor involvement in associative memory recall by generating and analyzing a genetically engineered mouse strain in which the N-methyl-d-asparate (NMDA) receptor gene is ablated specifically in the CA3 pyramidal cells of adult mice.

Pattern Separation in the Dentate Gyrus and CA3 of the Hippocampus

These results imply a dual mechanism for pattern separation in which signals from the entorhinal cortex can be decorrelated both by changes in coincidence patterns in the dentate gyrus and by recruitment of nonoverlapping cell assemblies in CA3.

CA1-specific N-methyl-d-aspartate receptor knockout mice are deficient in solving a nonspatial transverse patterning task

The results suggest that CA1 NMDA receptors play a crucial role in the encoding and flexible expression of stimulus relations in nonspatial memory.

Comparison of population coherence of place cells in hippocampal subfields CA1 and CA3

In a dynamically changing environment, in which familiar landmarks on the behavioural track and along the wall are rotated relative to each other, the population representation of the environment is more coherent between the original and cue-altered environments in CA3 than in CA1.

Long-term plasticity in hippocampal place-cell representation of environmental geometry

It is reported that, in rats repeatedly exposed to two differently shaped environments, the hippocampal-place-cell representations of those environments gradually and incrementally diverge; this divergence is specific to environmental shape.

CA3 NMDA receptors are crucial for rapid and automatic representation of context memory

It appears that rapid and automatic context memory representations from one‐time experience are mediated, at least in part, by CA3 NMDA receptors.