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New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory?

Key Points

  • The dentate gyrus in the hippocampus in one of the discrete regions in which new neurons are continuously generated and integrated into local networks in the brains of adult mammals, including humans. Studies in the past decade have led to an understanding of the process of neurogenesis in the dentate gyrus; however, the functions of adult-born dentate granule cells (DGCs) remain unclear.

  • After birth, adult-born DGCs undergo a lengthy process of morphogenesis including the de novo growth of axons and dendrites and the formation of both efferent and afferent synapses. The adult-born DGCs show enhanced excitability and plasticity before they are fully integrated into the brain circuitry.

  • The addition of adult-born DGCs into the local network is extensively regulated by the experiences of the animal, which evoke hippocampal activity. Physiological and pathological conditions that alter hippocampal activity also affect adult neurogenesis in the hippocampus. The experiences of animals, especially those occurring during the maturation of DGCs, can influence the responsiveness of these cells when they become fully mature.

  • A common hypothesis emerging from several computational studies is that adult neurogenesis allows plasticity to be mostly localized to newborn immature DGCs, preserving the information that is represented by mature DGCs. A recent model further proposes that immature DGCs can serve as a pattern integrator by linking events that occur closely in time.

  • Studies combining neurogenesis ablation models with behavioural analyses have yielded inconsistent data concerning the functions of adult hippocampal neurogenesis. Besides the differences in specific experimental conditions, the varied experimental timelines and the types of function assessed are two major reasons for these discrepancies.

  • The dentate gyrus plays a crucial role in pattern separation. A role for adult neurogenesis in pattern separation as a function of pattern similarity has recently been revealed.

  • In the future, novel methods that have the cellular and temporal precision to manipulate neurogenesis and behavioural tests that directly assess dentate gyrus-related functions will be required to understand the functional mechanisms of adult neurogenesis.

Abstract

The integration of adult-born neurons into the circuitry of the adult hippocampus suggests an important role for adult hippocampal neurogenesis in learning and memory, but its specific function in these processes has remained elusive. In this article, we summarize recent progress in this area, including advances based on behavioural studies and insights provided by computational modelling. Increasingly, evidence suggests that newborn neurons might be involved in hippocampal functions that are particularly dependent on the dentate gyrus, such as pattern separation. Furthermore, newborn neurons at different maturation stages may make distinct contributions to learning and memory. In particular, computational studies suggest that, before newborn neurons are fully mature, they might function as a pattern integrator by introducing a degree of similarity to the encoding of events that occur closely in time.

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Figure 1: The neural circuitry in the rodent hippocampus.
Figure 2: Adult hippocampal neurogenesis.
Figure 3: Computational theories of neurogenesis.

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Acknowledgements

We thank M. L. Gage for editorial comments. This work is funded by the James S. McDonnell Foundation, the Lookout Fund, the Kavli Institute for Brain and Mind, the NSF Temporal Dynamics of Learning Center, the US National Institutes of Health (NS-050217) and National Institute on Aging (AG-020938).

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Correspondence to Fred H. Gage.

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F.H.G. is on the scientific advisory boards of Stem Cell Inc., Ceregene Therapeutics and Brain Cells Inc.

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Glossary

Filopodia

Thin, long and highly motile protrusions that are the predecessors of spines in an early stage of spine formation.

Thorny excrescences

The complex spines on the dendrites of CA3 pyramidal neurons in the stratum lucidum. These spines form multiple synapses with mossy fibres of dentate granule cells.

Morris water maze (MWM)

A spatial learning paradigm in which an animal must learn a fixed location of a platform using distal spatial cues. Animals are released from a variable start point in each trial to encourage them to use a spatial strategy to solve the task.

BrdU birth-dating

The thymidine analogue bromodeoxyuridine (BrdU) is injected into adult animals and incorporated into cells synthesizing DNA in preparation for division, which are visualized using immunocytochemistry. Because the in vivo half-life of BrdU is 2 hours, it only labels dividing cells in a short time window.

Sparse coding

A type of neural code in which each event is encoded by the strong activation of a small set of neurons.

Attractor

A stable point in a dynamic system. Attractors are typically found in neural networks with strong feedback connections and are determined by the weights of the recurrent connections between units (neurons) in the network. Depending on the initial conditions and external inputs, the network will evolve towards one of these stable states.

Pattern integration

The ability of immature dentate granule cells to provide an association between events owing to their indiscriminate responses to inputs.

Pattern completion

A process by which a stored neural representation is reactivated by a cue that consists of a subset of that representation.

Trace conditioning

A form of classical conditioning in which the conditioned stimulus occurs before the unconditioned stimulus with a stimulus-free period (the 'trace interval' or 'conditioning interval') between the two.

Delay conditioning

A form of classical conditioning in which the onset of the conditioned stimulus precedes the onset of the unconditioned stimulus, with an overlap between the presentation of the conditioned stimulus and the presentation of the unconditioned stimulus.

Recognition memory

The ability to correctly remember something that has been previously encountered. It is a subcategory of declarative memory.

Contextual fear conditioning

A form of conditioning in which animals associate the conditioning context (the 'neutral' conditioned stimulus) with an aversive stimulus — for example, a foot shock.

Spatial discrimination

The ability to discriminate separate locations in space.

Conjunctive encoding

A form of information encoding in which a neuron requires the concurrent activity of multiple input neurons. In the hippocampus, dentate granule cells can associate spatial information from the medial entorhinal cortex with non-spatial information from the lateral entorhinal cortex to form a multi-dimensional representation of an event.

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Deng, W., Aimone, J. & Gage, F. New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory?. Nat Rev Neurosci 11, 339–350 (2010). https://doi.org/10.1038/nrn2822

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