Mechanisms of inhibitory processing in the olfactory bulb and its contribution to olfactory discrimination behavior
Final Report Abstract
The tandem project successfully developed, validated and applied a fully automated behavioral setup using group-housed mice. AutonoMouse was applied to assess the behavioral conseqeunces of olfactory bulb lesions, overproduction of granule cells and targeted molecular perturbations. We found that (1) GluA1 deletion yielded results identical with previous work using manual olfactometers, (2) damaged olfactory bulb can cope relatively easily with simple odour discrimination tasks and (3) an increased number of granule cells in the adult olfactory bulb only minimally improves odor discrimination. Opposite to the initial plan of deleting all iGluRs in granule cells, we examined the influence of inhibition on granule cell function and the role of sodium channels on GABA release. We found that granule cells receive inhibitory inputs that in turn modulate recurrent inhibition and thereby affect odor discrimination time. Furthermore, sodium channels could be demonstrated to mediate physiological release of GABA from granule cells, challenging the established model of NMDAR-dependent GABA release. In combination with earlier work these results established a quantitative relationship between the strenght of recurrent inhbition of mitral cells and odor discrimination time. Using in vivo whole-cell recordings in anaesthetized and awake mice we addressed the question how inhibitory circuits influence odour representation and which interneurons contribute to different physiological phenomena in the olfactory bulb. We found mitral and tufted cells both tightly lock to distinct but opposite phases of the sniff cycle, whose shift is established by inhibition in the OB. We also found that the baseline theta rhythm in the OB is structured by the local, glomerular inhibitory circuitry rather than from global, granule-cell mediated inhibition. Direct recordings from different juxtaglomerular neurons demonstrated the phase shift between mitral cell and tufted cell theta rhythms is set by a putative periglomeruar cell feedforward pathway. To distinguish the source of sniff-coupled inhibition, we employed layer-selective silencing of interneurons. In contrast to common belief, it turned out from theses experiments that the glomerular circuitry, likely via a feedforward inhibitory pathway, underlies evoked inhibition on slow timescales and potentially contrast enhancement. Consistent with previous models, granule cell silencing significantly reduced evoked power at gamma frequencies while theta oscillations remained unaffected.
Publications
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(2012) Psychophysical properties of odor processing can be quantitatively described by relative action potential latency patterns in mitral and tufted cells. Frontiers in systems neuroscience 6, 30
Schaefer AT, Margrie TW
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(2014) 'Silent' mitral cells dominate odor responses in the olfactory bulb of awake mice. Nature neuroscience 17, 1313-1315
Kollo M, Schmaltz A, Abdelhamid M, Fukunaga I, Schaefer AT
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(2014) Independent control of gamma and theta activity by distinct interneuron networks in the olfactory bulb. Nature neuroscience 17, 1208-1216
Fukunaga I, Herb JT, Kollo M, Boyden ES, Schaefer AT
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(2015) Disinhibition of olfactory bulb granule cells accelerates odor discrimination in mice. Nature Communications, 6:8950
Nunes D, Kuner T
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(2015) Divergent innervation of the olfactory bulb by distinct raphe nuclei. The Journal of comparative neurology 523, 805-813
Steinfeld R, Herb JT, Sprengel R, Schaefer AT, Fukunaga I
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(2016) Massive normalization of olfactory bulb output in mice with a 'monoclonal nose'. eLife 5
Roland B, Jordan R, Sosulski DL, Diodato A, Fukunaga I, Wickersham I, Franks KM, Schaefer AT, Fleischmann A
