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Physiological Status Promotes the Selective Activation of Regional Specific Adult Neural Stem Cells

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Review of “Hypothalamic regulation of regionally distinct adult neural stem cells and neurogenesis” from Science by Stuart P. Atkinson

In particular regions of the mammalian brain, neural stem cells (NSCs) can generate large numbers of more differentiated neural cells throughout adult life [1, 2]. NSCs of the subventricular zone (or SVZ) of the mammalian brain take on a regional identity, and according to this identity, produce different subtypes of neuronal cells [3]. 

A recent study from the laboratory of Fiona Doetsch (University of Basel, Switzerland) now indicates that neurons from a region of the brain dedicated to maintaining bodily homeostasis, the hypothalamus, make long-range contact with specific NSCs within the SVZ. Remarkably, this region-specific innervation promotes the activation of a subset of normally quiescent NSCs and the production of specific neuronal cell types as a consequence of physiological and environmental requirements [4].

Of the numerous types of neurons which innervate the cells within the SVZ, Paul et al. discovered that mouse hypothalamic proopiomelanocortin (POMC) neurons, which regulate feeding behavior [5, 6], made specific contact with the anterior-ventral part of the SVZ. Directed coomunication and innervation promoted the activation and proliferation of a particular subset of NSCs (Nkx2.1+) and the generation of deep granule cell layer (GCL) interneurons. 

To understand how physiological states can affect directly affect NSCs, the authors modulated POMC+ neuron activity via feeding (increased activity) and fasting (decreased activity). Interestingly, in vivo analysis demonstrated that altered feeding patterns altered Nkx2.1+ NSC proliferation via POMC+ neuron activity, so suggesting that physiological states sensed by the hypothalamus lead to specific alterations in NSC proliferation/neuron production via direct and specific innervation.

These findings indicate that distinct neuronal subtypes from other brain regions make regional-specific connections to SVZ-NSCs to alter their proliferation and, therefore, neuron-producing capacity; a mechanism through which physiological states can promote adult neurogenesis.

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References

  1. Fuentealba LC, Obernier K, and Alvarez-Buylla A. Adult neural stem cells bridge their niche. Cell Stem Cell 2012;10:698-708.
  2. Silva-Vargas V, Crouch EE, and Doetsch F. Adult neural stem cells and their niche: a dynamic duo during homeostasis, regeneration, and aging. Current opinion in neurobiology 2013;23:935-942.
  3. Chaker Z, Codega P, and Doetsch F. A mosaic world: puzzles revealed by adult neural stem cell heterogeneity. Wiley interdisciplinary reviews. Developmental biology 2016;5:640-658.
  4. Paul A, Chaker Z, and Doetsch F. Hypothalamic regulation of regionally distinct adult neural stem cells and neurogenesis. Science 2017;356:1383-1386.
  5. Zeltser LM, Seeley RJ, and Tschop MH. Synaptic plasticity in neuronal circuits regulating energy balance. Nat Neurosci 2012;15:1336-1342.
  6. Aponte Y, Atasoy D, and Sternson SM. AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training. Nat Neurosci 2011;14:351-355.