In most sensory modalities, neuronal connectivity reflects behaviorally relevant stimulus features, such as spatial location, orientation, and sound frequency. By contrast, the prevailing view in the olfactory cortex, based on the reconstruction of dozens of neurons, is that connectivity is random. Because piriform cortex circuits were assumed to be devoid of any innate structure, models of olfactory learning have assumed unstructured random connectivity, and were proposed to rely entirely on plasticity to construct meaningful representations.<\/p>\n
We recently revisited the question of the structure in the olfactory cortex circuit using high-throughput barcode sequencing-based single-cell projection mapping. These techniques include MAPseq and BARseq and analyzing the projections of 5,309 mouse olfactory bulb and 30,433 piriform cortex output neurons at single-cell resolution. Surprisingly, statistical analysis of this much larger dataset revealed that the olfactory cortex connectivity is spatially structured. Single olfactory bulb neurons targeting a particular location along the anterior-posterior axis of piriform cortex also project to matched, functionally distinct, extra-piriform targets. Moreover, single neurons from the targeted piriform locus also project to the same matched extra-piriform targets, forming triadic circuit motifs. For example, neurons in the olfactory bulb that target the anterior portion of the piriform cortex (aPCx) tend to project to the anterior olfactory nucleus (AON); and neurons in the targeted (anterior) piriform locus complete the triad by also projecting to the AON. Moreover, the same triadic organization is replicated at different positions within the piriform cortex, along its anterior-posterior axis, for other functionally distinct targets, such as the cortical amygdala (CoA) and lateral entorhinal cortex (lENT) via specific input-output projection gradients. As such, these results open the possibility that the olfactory cortex architecture is structured, and thus need not rely on algorithms that assume random connectivity. Similar to other sensory modalities, our data supports the view that olfactory information leaving the olfactory bulb is segregated in a coordinated manner into parallel processing streams that support different computations related to perception (OB-aPCx-AON), valence (OB-pPCx-CoA) and action (OB-pPCx-lENT).<\/p>\n
We aim to relate these putative triadic circuit motifs to the identity and functional properties of their input odorant receptors (ORs). In ongoing work, we are mapping the molecular identity of the ORs to their corresponding glomeruli on the bulb surface and determine OR sensitivities to large odor sets in vivo. Further, using BARseq and MAPseq, we map the brain-wide projections of mitral and tufted cells receiving input from specific glomeruli (ORs).<\/p>\n
Overall, we aim to establish a framework for relating the biophysical features of OR activation, the structure of the perceptual space and the underlying neural circuits.<\/p>\n
\nChae, et al. \u201cLong-range functional loops in the mouse olfactory system and their roles in computing odor identity.\u201d Neuron (2022). https:\/\/doi.org\/10.1038\/s41467-022-32267-3<\/a><\/div>\n
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