Rapid ongoing synaptogenesis in the adult brain

Olfactory sensory neurons are generated throughout life, but little is known about how these new neurons, which provide olfactory input to the brain, wire into existing neural circuits. We show that newly-generated olfactory sensory neurons can elicit responses in the brain earlier in their development than previously thought. Furthermore, we find that olfactory sensory neurons continuously form and eliminate synapses throughout their life cycle, enabling the brain to adapt constantly to changes in the odor environment.

HFSP Long-Term Fellow Claire Cheetham and colleagues
authored on Fri, 11 March 2016

In most brain regions, neurons assemble into circuits during embryonic and early postnatal development. In contrast, new neurons wire into circuits in the mammalian olfactory bulb throughout life. The olfactory bulb is the brain’s first processing station for odor information, and receives odor input from olfactory sensory neurons (OSNs) in the nose. OSN axons expressing the same odorant receptor coalesce to form glomeruli, thereby generating a highly organized odor map on the surface of the olfactory bulb. However, because OSNs are continuously generated throughout life, they must wire into pre-existing organized neural circuits without disrupting their function.

Figure: An olfactory bulb glomerulus in which mature OSN axons (magenta) and the synapses that they form (green) are genetically labelled. Using 2-photon time-lapse microscopy, we were able to track the formation and elimination of these synapses in real time in the living mouse brain.

When does a newly-generated OSN first become capable of synaptogenesis? Using genetic tools to specifically label populations of immature and mature OSNs in mice, we found that immature OSNs form synapses that are ultrastructurally indistinguishable from those formed by their mature counterparts. Furthermore, optogenetic stimulation of immature OSNs evoked functional responses in olfactory bulb neurons in vivo. Together, these findings suggest that newly-generated OSNs rapidly wire into olfactory bulb circuits, and hence could contribute to olfactory processing much earlier in their development than previously thought.

Whether OSNs retain the capacity for synaptogenesis once they have wired into the olfactory bulb has also never been investigated. To answer this question, we used in vivo 2-photon microscopy to watch the formation and elimination of OSN synapses in real time in the olfactory bulb. Immature OSNs formed and eliminated synapses very rapidly, consistent with them testing a large number of potential connections as they search for their postsynaptic targets. Surprisingly however, mature OSNs retained far higher levels of synapse formation and elimination than have been observed in other sensory brain areas. This rapid synaptic reorganization was strongly reduced when sensory input to OSNs was blocked.

While the olfactory system retains a high level of lifelong plasticity, the contribution of OSN replacement, which occurs on a timescale of weeks to months, to this plasticity has been unclear. We have uncovered a novel yet complementary plasticity mechanism that acts on a much faster timescale (hours to days): activity-dependent synaptogenesis and synapse elimination. This provides a sustained potential for tuning of odor preferences in response to environmental changes, and repair following damage.


Rapid and continuous activity-dependent plasticity of olfactory sensory input. Cheetham CE, Park U & Belluscio L. Nat Commun. 2016 Feb 22;7:10729. doi: 10.1038/ncomms10729.

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Link to full paper (open access)