Good ChAT: the brain controls neurogenesis from within

Researchers from Duke University have discovered a new type of neuron in the adult brain that can tell neural stem cells to proliferate into neurons.

These cells, a population of choline acetyltransferase positive (ChAT+) neurons, reside within the subventricular zone (SVZ) neurogenic niche. The ChAT enzyme is required to manufacture the neurotransmitter acetylcholine (Ach).

Chay Kuo, the George W Brumley Associate Professor at the Duke Institute for Brain Sciences and principle investigator of the study, said: "It is very unexpected and exciting to uncover this hidden gateway, a neural circuit that can directly instruct the stem cells to make more immature neurons."

The SVZ ChAT+ neurons are functionally and morphologically distinct from similar neurons in neighbouring brain regions and release ACh in an activity-dependent manner. Using optogenetics, Kuo and colleagues were able to modulate the firing frequency of the newly-found ChAT+ neurons. When these neurons activity increased there was also an increase in neural stem cell proliferation and the opposite was observed when activity decreased.

The research, featured on the front cover of Nature Neuroscience, found that these neurons were necessary and sufficient to control the production of new neurons in this niche.

The newly developed neurons were destined for the olfactory bulb of the mice used in this study, a part of the brain that needs new neurons to support learning in these animals. In humans, who have a much smaller and less active olfactory bulb, it is possible that these neurons are being produced for different brain regions.

The ChAT+ neurons are part of a mostly unknown brain circuit that seems to tell stem cells to increase new neuron production. Further research will need to concentrate on what brain signals tell ChAT+ neurons to start proliferation and how the stem cells respond to different frequencies of ChAT+ electrical activity.

Studies of stroke injury in rodents have spotted SVZ cells migrating into the neighbouring striatum. Researchers have also observed newly created neurons in the human striatum for the first time. Interestingly, in Huntington's disease patients, these neurons seem to be missing. The SVZ neurogenic niche may be responsible for helping maintain and repair this area.

Paper Reference:

Paez-Gonzalez P, Astrican B, Rodriguez E, Kuo CT (2014) Identification of distinct ChAT+ neurons and activity-dependent control of postnatal SVZ neurogenesis Nature Neuroscience 17: 934–942 doi: 10.1038/nn.3734