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

By T. McHugh, Matthew W. Jones, J. Quinn, N. Balthasar, R. Coppari, J. Elmquist, Bradford B. Lowell, M. Fanselow, Matthew A. Wilson, S. Tonegawa. 2007

978 citations recorded by the source corpus.

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 ability to distinguish two similar contexts. A significant reduction in the context-specific modulation of firing rate was observed in the CA3 pyramidal cells when the mutant mice were transferred from one context to another. These results provide evidence that NMDA receptors in the granule cells of the dentate gyrus play a crucial role in the process of pattern separation.

Subfields: Behavioral Neuroscience, Cellular and Molecular Neuroscience, Cognitive Neuroscience, Neuroscience

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Citations in the corpus

Re-evaluating circuit mechanisms underlying pattern separation (2019, positive): “For example, lesion and genetic deletion studies have shown that the dentate gyrus is necessary for the discrimination of similar contexts (Gilbert et al., 2001; McHugh et al., 2007; Hunsaker et al., 2008).”
Young dentate granule cells mediate pattern separation, whereas old granule cells facilitate pattern completion. (2012, neutral): “…given that previous theoretical and experimental work has suggested that the EC/ DG/CA3 pathway is crucial for pattern separation (Marr, 1971; McNaughton and Morris, 1987; Treves and Rolls, 1994; Gilbert et al., 2001; Leutgeb et al., 2007; McHugh et al., 2007; Hunsaker and Kesner, 2008) and…”
Gamma-band synchronization in the neocortex: novel analysis methods and their application to sensory and motivational systems (2013, background): “, 1995; Goosens & Maren, 2004), and in hippocampus in relation to spatial memory (Morris et al., 1986; Kentros et al., 1998; Ekstrom et al., 2001; McHugh et al., 2007), but not in the context of associative stimulus-reward learning as exemplified by OFC neurons.”
Memory engrams: Recalling the past and imagining the future (2020, background): “Stable place cells may be important in engrams supporting spatial or contextual memories (83-85).”
CA3 Retrieves Coherent Representations from Degraded Input: Direct Evidence for CA3 Pattern Completion and Dentate Gyrus Pattern Separation (2014, background): “…shown evidence consistent with a pattern separation function in both DG and CA3 and a pattern completion function in CA3 (e.g., Gilbert et al., 2001; Rolls and Kesner, 2006; Kesner et al., 2000; McHugh et al., 2007; Nakazawa et al., 2002; Lee et al., 2004; for review, see Yassa and Stark, 2011).”
Physiological properties and behavioral correlates of hippocampal granule cells and mossy cells (2017, positive): “In support of this hypothesis, damage to the dentate gyrus diminishes the animals’ ability to distinguish between similar environmental contexts, supporting its role in pattern separation (Gilbert et al., 2001; McHugh et al., 2007; Hunsaker et al., 2008; Kim and Lee, 2011; Nakashiba et al., 2012).”
Tonic Inhibitory Control of Dentate Gyrus Granule Cells by α5-Containing GABAA Receptors Reduces Memory Interference (2015, background): “Pattern separation has been suggested as a computational solution to the problem of interference in memory systems (McNaughton and Morris, 1987; O’Reilly and McClelland, 1994; Treves and Rolls, 1994; Kesner and Rolls, 2015).”
The mechanisms for pattern completion and pattern separation in the hippocampus (2013, background): “…spatial function (Rolls and Treves, 1998; Nakazawa et al., 2002, 2003; Wills et al., 2005; Rolls and Kesner, 2006; Kesner, 2007, 2013; Leutgeb et al., 2007; McHugh et al., 2007; Hunsaker and Kesner, 2008, 2013; Giocomo et al., 2011; Jezek et al., 2011; Kesner et al., 2012; Nakashiba et al., 2012).”
Synaptic Properties of SOM- and CCK-Expressing Cells in Dentate Gyrus Interneuron Networks (2014, background): “Its computational function involves the translation of multimodal patterns from the neocortex into sparse codes for the CA3 area (Treves and Rolls, 1994; Leutgeb et al., 2007; McHugh et al., 2007).”
Mechanisms and functional implications of adult neurogenesis. (2008, positive): “The pattern separation role of dentate gyrus has been recently demonstrated experimentally by either dentate gyrus-specific lesions or specific deletion of NMDA receptors in dentate gyrus (Gilbert et al., 2001; McHugh et al., 2007).”