We establish and experimentally validate a genetic in vivo axonal-competition paradigm in the mammalian CNS. By using this paradigm, we provide evidence for a specific effect of BDNF signaling on terminal-arbor pruning under competition in vivo. Our results have implications for the formation and refinement of the olfactory and other sensory maps, as well as for neuropsychiatric diseases and traits modulated by the BDNF val66met variant.
The mammalian olfactory system detects and discriminates thousands of odorants using many different receptors expressed by sensory neurons in the nasal epithelium. Axonal projections from these neurons to the main olfactory bulbs form reproducible patterns of glomeruli in two widely separated regions of each bulb, creating two mirror-symmetric maps of odorant receptor projections. To investigate whether odorant receptors organize neural circuitry in the olfactory bulb, we have examined a genetically modified mouse line, rI7 --> M71, in which a functionally characterized receptor, rI7, has been substituted into the M71 receptor locus. Here we show that despite their ectopic location the resulting glomeruli are responsive to known ligands of the rI7 receptor, attract postsynaptic innervation by mitral/tufted cell dendrites, and endow these cells with responses that are characteristic of the rI7 receptor. External tufted cells receiving input from rI7 --> M71 glomeruli form precise intrabulbar projections that link medial and lateral rI7 --> M71 glomeruli anatomically, thus providing a substrate for coordinating isofunctional glomeruli. We conclude that odorant receptor identity in epithelial neurons determines not only glomerular convergence and function, but also functional circuitry in the olfactory bulb.
In rodents, each main olfactory bulb contains two mirror-symmetric glomerular maps, a feature not found in the initial topographic maps of other sensory systems. Targeting tracer injections to identified glomeruli revealed that isofunctional odor columns-translaminar assemblies connected to a given glomerulus-were specifically and reciprocally interconnected through a mutually inhibitory circuit with exquisite topographic specificity. Thus, instead of containing two mirror-symmetric maps, we propose that the olfactory bulb contains a single integrated map in which isofunctional odor columns are connected through an intrabulbar link, analogous to the specific horizontal connections linking iso-orientation columns in primary visual cortex.
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