Processing of temporally dynamic olfactory input
Carey, Ryan Michael
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Odorant-evoked activity throughout the mammalian olfactory bulb (OB) is temporally dynamic and strongly shaped by sniffing behavior. Both olfactory receptor neurons (ORNs), which carry the first olfactory representations into the OB, and mitral/tufted (MT) cells, which project from the OB to the cortex, exhibit dynamic firing patterns organized around the respiratory cycle. These dynamics are thought to be important for odor coding, but remain poorly characterized, especially in the context of complex sniffing behaviors expressed by awake animals. Therefore, a central goal of this dissertation is to provide detailed characterizations of the temporal organizations ofORN inputs and MT outputs, and how these are modulated by sniffing. In addition, it explores how possible processing circuits might transform ORN inputs evoked during natural sniffing into patterns of postsynaptic MT activity. Three main experimental methods and one computational method were used. First, ORN inputs were characterized using optical imaging from awake, head-fixed rats. Second, extracellular recordings were obtained from MT cells in anesthetized rats while controlling sniffing with a novel "sniff playback" device. Third, a biophysical model of the early olfactory pathway was constructed to investigate how the ORN-MT transformation might be shaped by individual processing pathways. Finally, an optogenetic technique was used to selectively suppress activity in GABAergic interneurons, testing the effect of inhibitory pathways on MT responses during sniff playback. A principal finding is that sniff frequency is critically important for modulating OB activity. Slow sniffs during odorant presentation evoke bursts of activity in both ORN inputs and MT outputs. At higher sniff frequencies, ORN inputs attenuate and decorrelate from sniffing; however, MT outputs undergo a temporal sharpening, thereby maintaining strong respiratory patterning. The mechanism responsible for maintaining respiratory patterning across frequencies appears to involve the external tufted cell, a recently characterized interneuron that entrains to ORN inputs and may provide brief bursts of feedforward excitatory inputs to MT cells. Inhibitory interneurons modulate the overall excitability of MT outputs, but appear not to be critical in determining temporal response patterns. These results have important implications for odor coding, and provide insight into how natural sniffing may influence OB processing pathways.
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