Embryonic and postnatal neurogenesis produce functionally distinct subclasses of dopaminergic neuron

Elife. 2018 Apr 20:7:e32373. doi: 10.7554/eLife.32373.

Abstract

Most neurogenesis in the mammalian brain is completed embryonically, but in certain areas the production of neurons continues throughout postnatal life. The functional properties of mature postnatally generated neurons often match those of their embryonically produced counterparts. However, we show here that in the olfactory bulb (OB), embryonic and postnatal neurogenesis produce functionally distinct subpopulations of dopaminergic (DA) neurons. We define two subclasses of OB DA neuron by the presence or absence of a key subcellular specialisation: the axon initial segment (AIS). Large AIS-positive axon-bearing DA neurons are exclusively produced during early embryonic stages, leaving small anaxonic AIS-negative cells as the only DA subtype generated via adult neurogenesis. These populations are functionally distinct: large DA cells are more excitable, yet display weaker and - for certain long-latency or inhibitory events - more broadly tuned responses to odorant stimuli. Embryonic and postnatal neurogenesis can therefore generate distinct neuronal subclasses, placing important constraints on the functional roles of adult-born neurons in sensory processing.

Keywords: axon initial segment; development; dopamine; mouse; neurogenesis; neuroscience; olfactory bulb.

Plain language summary

Most of your brain cells were born before you were. But in mammals, including humans, some of these brain cells, also known as nerve cells or neurons, are created after birth. These later-generated neurons are often extremely similar to their counterparts produced in the womb, and also seem to perform a similar role once they are fully mature. However, it has not been entirely clear if the later-produced neurons may also have a specific purpose. Neurons are made of a cell body with a cable-like structure called axon that transmits information to more distant neurons, and dendrites, which are branches that receive information from other neurons. Neurons use different signalling molecules to communicate, one of which is called dopamine, and the neurons that use this specific signal are called dopaminergic neurons. Now, Galliano et al. wanted to test if neurons created in the womb, and neurons created after birth, are really so similar. To investigate this, they compared the dopaminergic neurons from mice found in the first part of the brain to process information about smell – the olfactory bulb. These specific neurons are known to have diverse properties and can also be produced after birth. Galliano et al. studied their development, form and purpose, and discovered that only neurons produced in the womb can possess an axon. Moreover, the axon-bearing cells had a different form and functional properties to their axon-less cousins, and also showed some subtle differences in their ability to respond to smell. This demonstrates that two very different types of dopaminergic neurons in the olfactory bulb are produced at different stages during the development. A better knowledge of such basic brain-developmental features is essential for the wider goal of understanding how the brain operates, and to discover ways to repair it when it is not working properly. Neurons created after birth in particular, might enable us to develop new treatment strategies; for example, adding new dopaminergic neurons to replace those lost in degenerative disorders such as Parkinson’s Disease. When developing such regenerative therapies, why not learn lessons from how the brain can achieve this naturally?

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axon Initial Segment / classification*
  • Dopaminergic Neurons / classification*
  • Dopaminergic Neurons / cytology*
  • Mice, Inbred C57BL
  • Neurogenesis*
  • Olfactory Bulb / embryology*
  • Phenotype