Our work centers on the mammalian olfactory bulb and the plasticity that is present within its neural circuitry. Our previous work has outlined specific components of that circuitry that we continue to analyze in response to sensory input and with respect to the broader network. We have recently been focusing on portions of the glomerular circuitry. While it is known that the glomerulus receives direct input from the nose via primary olfactory sensory neurons (OSNs) and that OSNs undergo continuous regeneration the dynamic aspects of their connectivity remain largely unexplored. In one study, we used a combination of techniques including electron microscopy, optogenetics and in vivo 2-photon-time-lapse imaging to follow the plasticity of OSN axons after they enter the glomerulus. Our findings showed that both newly arriving and fully mature OSN axons form highly dynamic synaptic connections that continuously remodel in an activity dependent manner (Cheetham et al, 2015). We suggest that this dynamic state may provide a mechanism for circuit reorganization that is more rapid and distinct from the regeneration process. We also engaged in a collaborative project to better understand odorant receptor (OR) gene regulation within OSNs. The study used a small promotor sequence to increase the number of OSNs expressing a given OR, thus causing increased sensitivity to specific odorants but with little disruption to OB connectivity (DHulst et al., 2015). This model will not only be useful for studying OR function in OSNs but also in understanding how OR activity drives the OB network. Within the glomerular circuitry Dopaminergic (DA) interneurons, which exhibit high levels of plasticity help modulate the transfer of olfactory information from OSNs to the OB output neurons. In another study we showed that microglia may play an important role in mediating DA neuron plasticity. Using in-vivo 2-photon time-lapse imaging we detected extensive microglial-neuronal interaction that was dependent upon odorant induced activity (Grier et al, 2016). Additional studies will be necessary to determine the precise role of microglia in regulating OB plasticity. To better understand the interaction between the various cell types within the glomerulus we have also developed a simple method to mark specific cell types called, Bulk Regional Viral Injection (BReVI), which can be applied to any Cre-expressing mouse line. This approach is fast, cost effective and can be used to target viral vectors directly to select brain regions in early postnatal animals (Cheetham, et al., 2015). This technique will enable a more extensive study of the glomerular network and its connections to other brain regions.
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