A Functional Role for Adult Hippocampal Neurogenesis in Spatial Pattern Separation

By C. Clelland, M. Choi, C. Romberg, Gregory D. Clemenson, A. Fragniere, P. Tyers, Sebastian Jessberger, L. Saksida, Roger A. Barker, Fred H. Gage and 1 more. 2009

1,676 citations recorded by the source corpus.

Neurogenesis and Spatial Memory The dentate gyrus of the hippocampus is one of two sites in the brain where new neurons are produced throughout life. Adult-born neurons integrate into the dentate gyrus circuitry and are thought to play a role in learning and memory. However, their contribution to hippocampal function remains unclear. Clelland et al. (p. 210) disrupted neurogenesis in mice and used two behavioral tasks to test for impairment in the formation of uncorrelated episodic memory representations. In one task, two arms were presented and the mice were rewarded for choosing the most recently visited arm in an earlier sequence; in the second task, animals were rewarded for choosing a certain location on a touch screen. Ablation of neurogenesis affected discrimination performance in both tasks but only when the arms or screen locations were close to one another. Neurogenesis is thus necessary for spatial pattern separation in the dentate gyrus. Disruption of neurogenesis in a neuron-forming site in the brain impairs spatial memory functions in mice. The dentate gyrus (DG) of the mammalian hippocampus is hypothesized to mediate pattern separation—the formation of distinct and orthogonal representations of mnemonic information—and also undergoes neurogenesis throughout life. How neurogenesis contributes to hippocampal function is largely unknown. Using adult mice in which hippocampal neurogenesis was ablated, we found specific impairments in spatial discrimination with two behavioral assays: (i) a spatial navigation radial arm maze task and (ii) a spatial, but non-navigable, task in the mouse touch screen. Mice with ablated neurogenesis were impaired when stimuli were presented with little spatial separation, but not when stimuli were more widely separated in space. Thus, newborn neurons may be necessary for normal pattern separation function in the DG of adult mice.

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

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Citations in the corpus

Generalization Through the Recurrent Interaction of Episodic Memories (2012, background): “…evidence points to a role in enhancing the orthogonalization capabilities of the DG, given that its disruption produces a specific impairment in paradigms where pattern separation demands are high (Becker, 2005; Clelland et al., 2009; Deng et al., 2010; Kempermann, 2002; Nakashiba et al., 2012).”
Dynamics of hippocampal neurogenesis in adult humans (2013, positive): “, 2004), which is critical for their role in mediating pattern separation in memory formation and cognition in rodents (Clelland et al., 2009; Nakashiba et al., 2012; Sahay et al., 2011).”
Adult hippocampal neurogenesis, Rho kinase inhibition and enhancement of neuronal survival. (2013, background): “…with regards to neurogenesis and some hippocampal dependent tasks, it is noteworthy that novel object recognition, which was unaltered in our paradigm, is not affected by ablation (Madsen et al., 2003, Rola et al., 2004, Clelland et al., 2009) or enhancement of neurogenesis (Sahay et al., 2011).”
Young dentate granule cells mediate pattern separation, whereas old granule cells facilitate pattern completion. (2012, positive): “Our current study combined with the recent studies focusing on the role of adult-born DG GCs (Clelland et al., 2009; Scobie et al., 2009; Tronel et al., 2012) provide several new concepts and clarifications regarding the function of the EC/DG/CA3 pathway in episodic memory.”
Early maternal deprivation affects dentate gyrus structure and emotional learning in adult female rats (2010, neutral): “These young, adult-born granule cells contribute significantly to behavioural functions such as contextual fear memory, spatial pattern separation and spatial learning (Clelland et al. 2009; Kitamura et al. 2009; Saxe et al. 2006).”
Resolving new memories: a critical look at the dentate gyrus, adult neurogenesis, and pattern separation (2011, methodology): “…tasks, animals were trained to learn one pattern and were subsequently tested, using a working memory framework, for their ability to discriminate a learned pattern from another pattern (Clelland et al., 2009; Creer et al., 2010; Gilbert et al., 2001; Hunsaker and Kesner, 2008; Saxe et al., 2007).”
Entorhinal Cortical Ocean Cells Encode Specific Contexts and Drive Context-Specific Fear Memory. (2015, positive): “, 2004) and dynamics of adult-born young granule cells which compose just a few percent of the total DG-GCs (Clelland et al., 2009; Creer et al., 2010; Deng et al., 2010; Nakashiba et al., 2012; Sahay et al., 2011; Scobie et al., 2009).”
Pattern Separation in the Dentate Gyrus: A Role for the CA3 Backprojection (2010, background): “…recent empirical data regarding selective DG manipulations support the idea that the DG is involved in pattern separation, particularly in tasks that require very similar stimuli to be distinguished (Gilbert et al., 2001; McHugh et al., 2007; Hunsaker et al., 2008; Clelland et al., 2009).”
An analysis of dentate gyrus function (an update) (2017, background): “Specifically, impairment occurred for arms that were presented with little separation, but no deficit was observed when the arms were presented farther apart [36], suggesting a spatial pattern separation R.”
Complementary Learning Systems (2014, positive): “…a variety of techniques (including multi-unit recordings in rats and high-resolution fMRI in humans) supports this pattern-separation theory (Bakker, Kirwan, Miller, & Stark, 2008; Clelland et al., 2009; Gilbert, Kesner, & Lee, 2001; Leutgeb, Leutgeb, Moser, & Moser, 2007; McHugh et al., 2007).”
Ablation of Fmrp in adult neural stem cells disrupts hippocampus-dependent learning (2011, neutral): “Improvements in hippocampal-dependent learning and decremental attention in 5-HT(3) receptor overexpressing mice.”
Adult-born hippocampal dentate granule cells undergoing maturation modulate learning and memory in the brain (2009, background): “Using chronic ablations of neurogenesis, a recent study suggested that an involvement of hippocampal neurogenesis in pattern separation (Clelland et al., 2009).”
Fragile X Mental Retardation Protein Regulates Proliferation and Differentiation of Adult Neural Stem/Progenitor Cells (2010, background): “More recent direct evidence has come from inducing the death of new neurons in the hippocampus [17–19] and from inhibiting the Wnt signaling pathway in the hippocampus using retrovirus [20].”
Neurogenesis in the striatum of the adult human brain. (2014, neutral): “Adult neurogenesis is important for pattern separation in memory formation and odor discrimination in rodents (Clelland et al., 2009; Nakashiba et al., 2012; Sahay et al., 2011), and alterations in adult neurogenesis are implicated in psychiatric disease in humans (Eisch and Petrik, 2012; Kheirbek e”