Beyond the Hippocampus and the SVZ: Adult Neurogenesis Throughout the Brain

Abstract

Convincing evidence has repeatedly shown that new neurons are produced in the mammalian brain into adulthood. Adult neurogenesis has been best described in the hippocampus and the subventricular zone (SVZ), in which a series of distinct stages of neuronal development has been well characterized. However, more recently, new neurons have also been found in other brain regions of the adult mammalian brain, including the hypothalamus, striatum, substantia nigra, cortex, and amygdala. While some studies have suggested that these new neurons originate from endogenous stem cell pools located within these brain regions, others have shown the migration of neurons from the SVZ to these regions. Notably, it has been shown that the generation of new neurons in these brain regions is impacted by neurologic processes such as stroke/ischemia and neurodegenerative disorders. Furthermore, numerous factors such as neurotrophic support, pharmacologic interventions, environmental exposures, and stem cell therapy can modulate this endogenous process. While the presence and significance of adult neurogenesis in the human brain (and particularly outside of the classical neurogenic regions) is still an area of debate, this intrinsic neurogenic potential and its possible regulation through therapeutic measures present an exciting alternative for the treatment of several neurologic conditions. This review summarizes evidence in support of the classic and novel neurogenic zones present within the mammalian brain and discusses the functional significance of these new neurons as well as the factors that regulate their production. Finally, it also discusses the potential clinical applications of promoting neurogenesis outside of the classical neurogenic niches, particularly in the hypothalamus, cortex, striatum, substantia nigra, and amygdala.

Keywords: adult neurogenesis; amygdala; cortex; hippocampus; hypothalamus; striatum; substantia nigra; subventricular zone.

Figure 1

Source of progenitor cells in different brain regions. The generation of new neurons from stem/progenitor cells has been extensively described in the hippocampal dentate gyrus (DG) and the subventricular zone/olfactory bulb (SVZ/OB). In the DG, precursor cells located in the subgranular zone divide and give rise to amplifying cells, which can commit to a neuronal phenotype and move into the granule cell layer to integrate into existing hippocampal circuitries. Similarly, dividing progenitor cells in the SVZ can differentiate into neural progenitors and migrate through the rostral migratory stream (RMS) towards the OB. Besides these two regions, there is emerging evidence indicating that the hypothalamic arcuate nucleus and the median eminence present neurogenic capacity. Particularly, a subpopulation of tanycytes has been shown to display neurogenic characteristics in these subregions. Additionally, experimental evidence has suggested that progenitor cells can deviate from the RMS and differentiate and mature into other brain regions including the prefrontal cortex, striatum, substantia nigra, and amygdala.

Figure 2

Functional implications of adult neurogenesis. The contribution of adult neurogenesis to physiological and pathological processes mediated by the hippocampus and the OB is supported by a substantial amount of evidence from rodent studies. In the hippocampus, this process regulates specific aspects of cognitive (dorsal portion) and affective (ventral portion) processing, while newborn neurons generated in the SVZ were shown to contribute to olfactory function and reproductive behavior (in birds). There is also increasing evidence indicating that neural progenitors may exert a relevant role in the regulation of hypothalamic function (particularly in metabolic function/feeding behaviors). On the other hand, it is still unclear whether progenitor cells found in other brain regions have a functional significance other than participating in recovery processes triggered following injury, neuronal loss, or neurodegeneration.