Modulating Neuronal Competition Dynamics in the Dentate Gyrus to Rejuvenate Aging Memory Circuits

McAvoy, Kathleen M.; Scobie, Kimberly N.; Berger, Stefan; Russo, Christopher J.; Guo, Nannan; Decharatanachart, Pakanat; Vega-Ramirez, Hugo; Miake-Lye, Sam; Whalen, Michael J.; Nelson, Mark L.; Bergami, Matteo; Bartsch, Dušan; Hen, René; Berninger, Benedikt; Sahay, Amar

doi:10.1016/j.neuron.2016.08.009

Cited by 144 publications

(171 citation statements)

References 77 publications

(97 reference statements)

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“…There is considerable evidence that the ability to discriminate between overlapping stimulus elements (pattern separation), is associated with hippocampal function (Leutgeb et al, 2007) and, in particular, adult neurogenesis in DG (Clelland et al, 2009; Abrous and Wojtowicz, 2016; McAvoy et al, 2016). The present results extend previous reports by showing that adult neurogenesis can be enhanced by early experience and, as a mechanism underlying pattern separation, can be mediated through a build-up of cognitive reserve.…”

Section: Discussionmentioning

confidence: 99%

Early-Age Running Enhances Activity of Adult-Born Dentate Granule Neurons Following Learning in Rats

Shevtsova

Tan

Merkley

et al. 2017

eNeuro

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Cognitive reserve, the brain’s capacity to draw on enriching experiences during youth, is believed to protect against memory loss associated with a decline in hippocampal function, as seen in normal aging and neurodegenerative disease. Adult neurogenesis has been suggested as a specific mechanism involved in cognitive (or neurogenic) reserve. The first objective of this study was to compare learning–related neuronal activity in adult-born versus developmentally born hippocampal neurons in juvenile male rats that had engaged in extensive running activity during early development or reared in a standard laboratory environment. The second objective was to investigate the long-term effect of exercise in rats on learning and memory of a contextual fear (CF) response later in adulthood. These aims address the important question as to whether exercise in early life is sufficient to build a reserve that protects against the process of cognitive aging. The results reveal a long-term effect of early running on adult-born dentate granule neurons and a special role for adult-born neurons in contextual memory, in a manner that is consistent with the neurogenic reserve hypothesis.

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Section: Discussionmentioning

confidence: 99%

Early-Age Running Enhances Activity of Adult-Born Dentate Granule Neurons Following Learning in Rats

Shevtsova

Tan

Merkley

et al. 2017

eNeuro

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“…Accordingly, increasing the number of adult-born neurons 84–87 or their functional integration into the dentate gyrus microcircuit 88 enhances the ability to discriminate highly similar contexts. By contrast, discriminating contexts that are very different (low interference) is not dependent on neurogenesis 37,51,77,84,85,89 .…”

Section: Neurogenesis Learning and Memorymentioning

confidence: 99%

Adult hippocampal neurogenesis and cognitive flexibility — linking memory and mood

2017

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Adult hippocampal neurogenesis has been implicated in cognitive processes, such as pattern separation, and in the behavioural effects of stress and antidepressants. Young adult-born neurons have been shown to inhibit the overall activity of the dentate gyrus by recruiting local interneurons, which may result in sparse contextual representations and improved pattern separation. We propose that neurogenesis-mediated inhibition also reduces memory interference and enables reversal learning both in neutral situations and in emotionally charged ones. Such improved cognitive flexibility may in turn help to decrease anxiety-like and depressive-like behaviour.

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“…A recent review suggests that an improvement in pattern separation, particularly for situations that are emotionally arousing, may affect mood and anxiety symptoms as well 141 . The effect of DG neurogenesis on pattern-separation computations in healthy and disease- affected populations is an important avenue of future investigation, particularly as rodent studies have identified a role for adult-born neurons in population-based coding in DG 14 and CA3 142 . Recent studies using nuclear-bomb-test-derived 14 C suggest high levels of turnover in the human DG 143 , indicative of a continuous role for adult neurogenesis.…”

Section: Psychostimulants and Pharmacological Agentsmentioning

confidence: 99%

Integrating new findings and examining clinical applications of pattern separation

2018

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Pattern separation, the ability to independently represent and store similar experiences, is a crucial facet of episodic memory. Growing evidence suggests that the hippocampus possesses unique circuitry that is computationally capable of resolving mnemonic interference by using pattern separation. In this Review, we discuss recent advances in the understanding of this process and evaluate the caveats and limitations of linking across animal and human studies. We summarize clinical and translational studies using methods that are sensitive to pattern separation impairments, an approach that stems from the fact that the hippocampus is a major site of disruption in many brain disorders. We critically evaluate the assumptions that guide fundamental and translational studies in this area. Finally, we suggest guidelines for future research and offer ways to overcome potential interpretational challenges to increase the utility of pattern separation as a construct that can further understanding of both memory processes and brain disease.

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Modulating Neuronal Competition Dynamics in the Dentate Gyrus to Rejuvenate Aging Memory Circuits

Cited by 144 publications

References 77 publications

Early-Age Running Enhances Activity of Adult-Born Dentate Granule Neurons Following Learning in Rats

Early-Age Running Enhances Activity of Adult-Born Dentate Granule Neurons Following Learning in Rats

Adult hippocampal neurogenesis and cognitive flexibility — linking memory and mood

Integrating new findings and examining clinical applications of pattern separation

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