Olfactory information is first processed by the neural circuits in the olfactory bulb. It is now widely appreciated
that the olfactory bulb circuit is modified in an experience-dependent manner. An especially dramatic example
of plasticity in olfactory bulb circuits is adult neurogenesis, in which thousands of newly born neurons are
incorporated into the bulbar circuitry as local inhibitory neurons every day throughout adulthood. The majority
of these adult-born neurons (ABNs) become granule cells that provide inhibition through the spines at their
apical dendrites onto the principal mitral/tufted cells. In this proposal, we will characterize the synaptic
structural plasticity of ABNs in the olfactory bulb and investigate its context-specificity and mechanisms.
Understanding the detailed mechanisms of context-specific plasticity would have an important impact on
clinical disorders such as Alzheimer's disease, age-related dementia, and post-traumatic stress disorders. Our
central hypotheses are that 1) ABNs increase the density of their apical dendritic spines during
learning of an olfactory discrimination task but not during passive experience of the same odorants,
and 2) this context-specificity of ABN plasticity is ensured by feedback projections from the piriform
cortex to the olfactory bulb which increases dendritic activity of ABNs during task learning. Such a
context-specific recruitment of ABN inhibition could provide the basis for stimulus-specific inhibition to promote
the pattern separation of representations of task-relevant odorants.
We will address these hypotheses by combining in vivo two-photon structural imaging, in vivo two-
photon calcium imaging, behavioral task in head-fixed mice, and pathway-specific optogenetics. We have been
pioneering the use of these techniques in studying the dynamics of olfactory bulb circuits (Kato et al. Neuron
2012, Kato et al. Neuron 2013, Boyd et al. Cell Reports 2015, Chu et al. Neuron 2016, Chu et al. eNeuro 2017).
In particular, we will leverage on our recent study that showed that ABNs are uniquely required for the learning
of fine olfactory discrimination (Li et al. eLife 2018). In Aim 1, we will investigate the age- and context-
specificity of granule cell synaptic plasticity in vivo and test the hypothesis that young ABNs uniquely increase
their spine density during learning. In Aim 2, we will examine the dendritic calcium activity of ABNs as a
potential cellular mechanism regulating ABN dendritic plasticity. In Aim 3, we will address the role of feedback
projections from the piriform cortex to the olfactory bulb as a potential circuit mechanism that ensures the
context specificity of ABN plasticity. These aims represent a systematic approach to investigate the
mechanisms of how behavioral context can affect the plasticity of an olfactory circuit.