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Jun 3, 2014

Neurons Signal Stem Cells to Make New Neurons

Neurons Signal Stem Cells to Make New Neurons

In the adult subependymal neurogenic niche, electrical signals generated by the ChAT+ neuron give rise to newborn migrating neuroblasts. [Duke University/O'Reilly Science Art]

  • Although neuroscientists have long suspected that the brain has some capacity to generate new neurons, they have struggled to uncover details of the brain’s capacity for repair and, possibly, self-improvement. Neuroscientists surmised that new neurons emerge when stem cells activate certain internal processes in response to environmental cues. But neuroscientists were still unsure what the nature of these cues might be. Now, as a result of a study from Duke, it has been found that neural stem cells respond to signals emitted by adult neurons.

    In effect, the stem cells respond to requests by adult neurons for additional neurons. The adult neurons, report the Duke researchers, constitute a previously unidentified population of choline acetyltransferase (ChAT)+ neurons. Because the neurons reside in the mouse subventricular (SVZ) neurogenic niche, prime real estate around the lateral ventricles, the researchers speculate that it may serve as a kind of factory, fulfilling orders needed to help the learning brain keep up with new tasks.

    In the Duke study, which was summarized June 1 in Nature Neuroscience (“Identification of distinct ChAT+ neurons and activity-dependent control of postnatal SVZ neurogenesis”), newly produced neurons were destined for the olfactory bulb, which occupies a fairly large portion of the mouse brain, accounting for the mouse’s ability to process the sense of smell. New neurons in the olfactory bulb could help support the learning of new scents.

    In humans, who have a much less impressive olfactory bulb, it’s possible that new neurons are produced for other brain regions. One such region may be the striatum, which mediates motor and cognitive controls between the cortex and the complex basal ganglia.

    The emergence of neuroregenerative mechanisms have the researchers hopeful that it may be possible to engage certain circuits of the brain to lead to a “hardware upgrade.” The study’s lead author, Chay Kuo, M.D., Ph.D., remarked, “Wouldn't it be nice if you could upgrade the brain hardware to keep up with the new software?” He added perhaps there will be a way to combine behavioral therapy and stem cell treatments after a brain injury to rebuild some of the damage.

    To return to the details of the study, it should be noted that the researchers established that varying the firing frequency of ChAT+ neurons, via optogenetic inhibition and stimulation, was “necessary and sufficient” to control the production of new neurons from the SVZ niche. “These neurons showed morphological and functional differences from neighboring striatal counterparts and released acetylcholine locally in an activity-dependent fashion," wrote the authors. "Furthermore, whole-cell recordings and biochemical experiments revealed direct SVZ NSC responses to local acetylcholine release, synergizing with fibroblast growth factor receptor activation to increase neuroblast production.”

    The questions ahead are both upstream from the new ChAT+ neurons and downstream, Dr. Kuo said. Upstream, what brain signals tell ChAT+ neurons to start asking the stem cells for more young neurons? Downstream, what's the logic governing the response of the stem cells to different frequencies of ChAT+ electrical activity?
     
    There's also the issue of somehow being able to introduce new components into an existing neuronal circuit, a practice that parts of the brain might normally resist. "I think that some neural circuits welcome new members, and some don't," Dr. Kuo mused.

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