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Adult neurogenesis and functional plasticity in neuronal circuits

Nature Reviews Neuroscience volume 7, pages 179–193 (2006)Cite this article

Key Points

  • The adult brain is a plastic place. Neuronal responses to a changing environment can occur at the level of molecules, spines, dendrites, axons and, with processes of adult neurogenesis, at the level of entire cells.

  • Neurogenesis definitely occurs in two regions of the adult brain: the subventricular zone (SVZ) lining the lateral ventricle and the subgranular zone (SGZ) of the dentate gyrus in the hippocampus.

  • Neuroblasts from the SVZ migrate along the rostral migratory stream (RMS) to provide new inhibitory granule cells and glomerular cells in the olfactory bulb. Newborn cells from the SGZ migrate to the granular layer of the dentate gyrus, where most of them become excitatory granule cells.

  • The functional maturation of adult-born cells always involves the expression of neurotransmitter receptors before synaptic activity, and the presence of (excitatory) GABA (γ-aminobutyric acid)-mediated influences prior to glutamatergic input. But other maturational features depend on specific cell types, with, for example, olfactory bulb granule cells being late to develop sodium-based action potentials.

  • Factors intrinsic to adult-born cells influence many facets of their maturation. Proliferation and cell fate decisions are particularly strongly controlled by the proteins expressed by neuroblasts.

  • Factors extrinsic to adult-born cells also have a huge influence on all processes of neurogenesis. In this way, adult neurogenesis represents another weapon in the brain's plasticity armoury for dealing with a constantly changing world.

  • With respect to its possible functions, adult neurogenesis might alter the olfactory bulb and hippocampus at the cellular, network and system levels. Computational models suggest that cell turnover might be especially beneficial for the learning of new information.

  • Definitive experiments to demonstrate the function(s) of adult neurogenesis await manipulations that can specifically and completely eliminate it. However, numerous lines of correlative and intervention evidence suggest that hippocampal neurogenesis might be crucial for spatial learning, and that olfactory bulb neurogenesis could be important for sensory discrimination.

Abstract

The adult brain is a plastic place. To ensure that the mature nervous system's control of behaviour is flexible in the face of a varying environment, morphological and physiological changes are possible at many levels, including that of the entire cell. In two areas of the adult brain — the olfactory bulb and the dentate gyrus — new neurons are generated throughout life and form an integral part of the normal functional circuitry. This process is not fixed, but highly modulated, revealing a plastic mechanism by which the brain's performance can be optimized for a given environment. The functional benefits of this whole-cell plasticity, however, remain a matter for debate.

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Figure 1: Postmitotic maturation of newborn neurons in the adult brain.
Figure 2: Intrinsic programmes and external factors controlling adult neurogenesis in the subventricular zone.
Figure 3: Intrinsic programmes and external factors controlling adult neurogenesis in the dentate gyrus.
Figure 4: Possible functions of newborn neurons at the cellular and network levels.

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Acknowledgements

This work was supported by the Pasteur Institute (GPH 'stem cells'), the Fondation pour la Recherche Médicale, the Association Française Contre les Myopathies, the Fédération pour la Recherche sur le Cerveau and a grant from Région Ile-de-France (all in France). We apologize to those authors whose references, although relevant to this subject, have not been included in this review owing to space constraints.

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  1. Laboratory of Perception and Memory, Institut Pasteur, Centre National de la Recherche Scientifique Unit de Recherche Associée 2182, 25, rue du Docteur Roux, Paris, 75724, Cedex 15, France

    Pierre-Marie Lledo, Mariana Alonso & Matthew S. Grubb

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  1. Pierre-Marie Lledo
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  2. Mariana Alonso
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Correspondence to Pierre-Marie Lledo.

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FURTHER INFORMATION

Perception and Memory Laboratory (Pasteur Institute)

Glossary

Adult neurogenesis

The entire set of events leading to the production of new neurons in the adult brain, from precursor cell division to functionally integrated survival.

Precursors

CNS stem cells and all progenitors are generally referred to as precursor cells.

Progenitor

A mitotic cell with a fast cell-division cycle that retains the ability to proliferate and to give rise to terminally differentiated cells but that is not capable of indefinite self-renewal.

Retrovirus

An RNA virus that uses reverse transcriptase to convert its RNA into DNA.

Neurogenic niche

Regions where the degree of neurogenesis depends on the interaction of the microenvironment with precursor cells that have neurogenic potential.

Antisense oligodeoxynucleotide

A small deoxynucleotide that is complementary to a select region of the mRNA that encodes the protein of interest. It can potentially interfere with transcription and translation, thereby decreasing gene expression. These molecules have been used in vivo to selectively inhibit the expression of peptides and proteins in the brain. This provides a simple way of studying the effects of the absence of a gene product in simple organisms and in cells.

Stereological analyses

Classic stereology microscopy has developed along independent pathways as a methodology to provide a quantitative understanding of the structure of the brain. This type of analysis has concentrated on the unbiased numerical estimation of parameters such as length, area, volume and population size that characterize entire regions of the brain as well as individual elements within them, for example, cell volume.

Trace eyeblink conditioning

A hippocampus-dependent task in which animals must associate a conditioned stimulus with an eyeblink-producing unconditioned stimulus. The key 'trace' aspect comes from the fact that the two stimuli are separated in time.

Morris water maze

In its most common form, a test of spatial learning and memory, in which animals must use spatial cues to locate a hidden platform in a pool of opaque water.

Long-term potentiation

(LTP). An enduring increase in the amplitude of excitatory postsynaptic potentials as a result of high-frequency (tetanic) stimulation of afferent pathways. LTP is often considered to be the cellular basis of learning and memory in vertebrates.

Barnes maze

In its most common form, a challenging test of spatial learning and memory. Animals must locate a single escape tunnel hidden under one of 40 possible entrance holes.

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Lledo, PM., Alonso, M. & Grubb, M. Adult neurogenesis and functional plasticity in neuronal circuits. Nat Rev Neurosci 7, 179–193 (2006). https://doi.org/10.1038/nrn1867

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