Adult Neurogenesis: From Precursors to Network and Physiology

Abstract

The discovery that the adult mammalian brain creates new neurons from pools of stemlike cells was a breakthrough in neuroscience. Interestingly, this particular new form of structural brain plasticity seems specific to discrete brain regions, and most investigations concern the subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampal formation (HF). Overall, two main lines of research have emerged over the last two decades: the first aims to understand the fundamental biological properties of neural stemlike cells (and their progeny) and the integration of the newly born neurons into preexisting networks, while the second focuses on understanding its relevance in brain functioning, which has been more extensively approached in the DG. Here, we propose an overview of the current knowledge on adult neurogenesis and its functional relevance for the adult brain. We first present an analysis of the methodological issues that have hampered progress in this field and describe the main neurogenic sites with their specificities. We will see that despite considerable progress, the levels of anatomic and functional integration of the newly born neurons within the host circuitry have yet to be elucidated. Then the intracellular mechanisms controlling neuronal fate are presented briefly, along with the extrinsic factors that regulate adult neurogenesis. We will see that a growing list of epigenetic factors that display a specificity of action depending on the neurogenic site under consideration has been identified. Finally, we review the progress accomplished in implicating neurogenesis in hippocampal functioning under physiological conditions and in the development of hippocampal-related pathologies such as epilepsy, mood disorders, and addiction. This constitutes a necessary step in promoting the development of therapeutic strategies.

Neuronal distribution of Spatial in the developing cerebellum and hippocampus and its somatodendritic association with the kinesin motor KIF17

“…In contrast, Spatial is detected in post-mitotic granule cells that continuously migrate and differentiate into mature neurons to form the superficial granule layer [20]. This particular expression in granule cells during differentiation reinforces the hypothesis that Spatial is involved in neuronal morphogenesis which also continues in the adult [20]. In addition, mRNA and biochemical analyses of Spatial expression during hippocampal development are in agreement with a potential involvement of Spatial isoforms in morphogenesis.…”

“…Proliferating cells in the subgranular layer located on the inner side do not express Spatial. In contrast, Spatial is detected in post-mitotic granule cells that continuously migrate and differentiate into mature neurons to form the superficial granule layer [20]. This particular expression in granule cells during differentiation reinforces the hypothesis that Spatial is involved in neuronal morphogenesis which also continues in the adult [20].…”

Cellular Therapy and Induced Neuronal Replacement for Huntington's Disease

“…In mammals, neural stem cells of the subventricular zone (SVZ) continually generate transit-amplifying glial and neuronal daughters, at least some of which give rise to new neurons [67][68][69][70]; the latter are typically recruited anteriorly to the olfactory bulb as GABAergic interneurons of several phenotypes [68,[71][72][73][74][75]. Olfactory neuronal recruitment is rapid; in mice, it takes approximately 15 days for neuronally restricted progenitor cells of the SVZ to migrate through the rostral migratory stream to the olfactory bulb, traversing a distance of 3 to 5 mm, wherein they differentiate into olfactory interneurons [67,76,77] (for more detail see Whitman and Greer [78] and Abrous et al [79]). In addition, some neural stem cells migrate posteriorly in development to form a separate germinal neuroepithelium, the subgranular zone of the hippocampal dentate gyrus [80][81][82][83].…”

Direct Evidence of Astrocytic Modulation in the Development of Rewarding Effects Induced by Drugs of Abuse

“…Both in vitro and in vivo studies have documented the ability of astrocytes to produce interleukin-1, -6, and -10; interferon-a, and -b; colony-stimulating factors GM-CSF, M-CSF, and G-CSF; TNF-a; TGF-b; and chemokines (Dong and Benveniste, 2001). Accumulating evidence suggests that astrocytes may actively participate in synaptic plasticity (Ullian et al, 2004;Abrous et al, 2005).…”