UC San Diego

Stem cells that have the potential of proliferation are commonly seen in lower animals, as well as certain tissues in mammals such as the skin tissue or liver tissue. The mammalian brain, as a highly differentiated and complex organ, however, was thought to consist only post-mitotic neurons. Findings in recent decades have confirmed that, in mammals like rodents or human beings, neurons are continuously generated throughout the adulthood by stem cells residing in specific niches of the brain. One of the two major niches is the sub-ventricular zone, from where newly generated neurons migrate through the rostral migratory stream and arrive almost exclusively at the olfactory bulb (OB), the first olfactory information processing center.

Mice were used to study the role of adult-born neurons (ABNs) in olfaction. As creatures constantly exposed to complex olfactory stimuli and relying on olfaction to survive, their OB needs sufficient capacity to encode olfactory information, for example, discriminating highly similar stimuli. Olfactory information is converged in the OB, and then relayed by mitral cells (MCs), the excitatory principal neurons in the OB, to higher brain areas. Interneurons, mainly consisting of periglomerular cells (PGCs) and granule cells (GCs), do not send long-range projections, but to modulate activities of MCs. Such modulation is considered the key of plasticity of the OB in decoding and encoding olfaction information. More interestingly, interneurons receive centrifugal projections from multiple higher brain areas as well as neuromodulatory inputs, which make them ideal candidates to mediate top-down control of the olfactory perception. One widely studied top-down influence on peripheral sensory areas is related to the behavioral state.

Once entering the OB, ABNs develop into interneurons, and, within a critical period, display higher plasticity and morphological dynamics. These features indicate that ABNs are specially important in olfactory information processing. To investigate the role of ABNs, I used a genetic method to specifically ablate ABNs. The effect of missing ABNs on olfactory perception was studied using carefully designed behavioral tasks, and with the longitudinal two-photon microscopy technique, changes in MCs olfactory encoding in the absence of ABNs were discovered.