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Abstract:
To maintain a functional mitochondrial population in a long-lived cell like a neuron, mitochondria must be continuously replenished through the process of mitochondrial biogenesis. Because the majority of mitochondrial proteins are nuclear encoded, mitochondrial biogenesis requires communication between mitochondria and the nucleus. This can be a challenge in a large, compartmentalized cell like a neuron in which a large portion of the mitochondrial population is in neuronal compartments far from the nucleus. Using in vivo assessments of mitochondrial biogenesis in zebrafish neurons, we determined that mitochondrial transport between distal axonal compartments and the cell body is required for sustained mitochondrial biogenesis. Estrogen-related receptor transcriptional activation links transport with nuclear expression of mitochondrial genes. New data suggests this regulation supports cell body based and local mitochondrial biogenesis at the synapse which we hypothesize work together to support distal mitochondrial populations. Together, our data support a role for retrograde feedback between axonal mitochondria and the nucleus for regulation of mitochondrial biogenesis in neurons.
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Abstract: Odors – chemical signals from the environment – are primary sensory drivers of behavior in most animal species and provide information essential to survival. In mammals, olfactory sensation is linked to inhalation, which delivers external odorants to olfactory sensory neurons (OSNs). There is strong evidence that both the identity of OSNs activated by an odorant and their timing of activity relative to inhalation are important features of the neural mechanisms underlying olfactory sensation, but how such features are determined by odor identity, odor concentration and odor sampling (i.e., inhalation) remains unclear. In this seminar, I will review work from our laboratory that characterizes the determinants of OSN responses across a large fraction of the sensory neuron population in vivo, as well as the transformation of sensory input patterns by olfactory bulb circuitry. This work has led to the surprising conclusion that the rapid conversion of one odorant to another by nasal enzymes profoundly shapes neural representations of odor identity and underlies much of the diversity in temporal dynamics of sensory responses. I will discuss the implications of these results for reconsidering the role of timing in odor coding and the potential for external versus internally-generated odors to differentially drive sensation and behavior.
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