Distant Brain Regions Selectively Recruit Stem Cells

    Long-distance connections in the adult brain may dial up stem-cell niches and order the delivery of particular types of neurons. Of all the brain’s stem-cell niches, the largest is the ventricular–subventricular zone (V-SVZ), which supplies neurons to the olfactory bulb. While the olfactory bulb’s densely interwoven network of neurons has been known to be important for distinguishing odors, it may also play a role in recruiting distinct neural stem cell (NSC) pools. That is, olfactory stimuli, in response to environmental and physiological signals, may drive “on-demand” adult neurogenesis.

    Not to be put off the scent of a new discovery, scientists based at the University of Basel observed that in mice, long-distance brain connections can target discrete pools of stem cells in a particular niche and stimulate them to divide and produce specific subtypes of olfactory bulb neurons. This allows the “on-demand” generation of particular types of neurons in the adult brain.  These scientists, led by Fiona Doetsch, Ph.D., reported their results June 15 in the journal Science, in an article entitled, “Hypothalamic Regulation of Regionally Distinct Adult Neural Stem Cells and Neurogenesis.”

    “Hypothalamic proopiomelanocortin (POMC) neurons selectively innervate the anterior ventral V-SVZ and promote the proliferation of Nkx2.1⁺ NSCs and generation of deep granule neurons,” wrote the authors of the Science article. “Accordingly, hunger and satiety regulate adult neurogenesis by modulating the activity of this hypothalamic-V-SVZ connection.”

    Our brain generates new neurons throughout life. A diversity of stimuli promotes stem cells in their niches to form neurons that migrate to their places of action.

    In the SVZ, quiescent stem cells lie closely packed together, and each of these stem cells has its own identity, depending on its location. “NSCs in the adult mouse V-SVZ exhibit a regional identity,” the authors noted, “and depending on their location, generate distinct olfactory bulb interneuron subtypes.”

    Although new neurons are continuously generated by the mouse V-SVZ—almost 100,000 each day—whether niche signals act to control different pools of stem cells has been unknown. Yet niche signals, the new results suggest, emanate from the hypothalamus and provide long-range regionalized input to the V-SVZ niche to regulate specific NSC subpopulations.

    “We have uncovered a novel long-distance and regionalized connection in the brain between the hypothalamus and the subventricular zone,” notes Prof. Doetsch, “and show that physiological states such as hunger and satiety can regulate the recruitment of specific pools of stem cells and in turn the formation of certain neuron subtypes in the olfactory bulb.”

    When the animals fasted, the activity of the nerve cells in the hypothalamus decreased and with it also the rate of proliferation in the targeted stem cell population. This activity returns to normal levels when the animals feed again. The division of stem cells can be controlled by changing the activity of feeding-related neurons.

    The researchers reported further that the targeted stem cell subpopulation gives rise to deep granule cells in the olfactory bulb, which may provide a substrate for adaptive responses to the environment. The results of the study raise the exciting possibility that neural circuits from diverse brain regions can regulate different pools of stem cells in response to various stimuli and states.