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Monday, July 20 • 8:00pm - 9:00pm
P30: Biophysically Realistic Model of Mouse Olfactory Bulb Gamma Fingerprint

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Abstract Figure 1 | "Poster" Slides | Model Website | Model Source Code | Model Documentation | 3D Interactive Model Visualization

Justas Birgiolas
, Richard Gerkin, Sharon Crook

The mammalian olfactory bulb is an intensively investigated system that is important in understanding neurodegenerative diseases. Insights gained from understanding the system also have important agricultural and national security applications. In this work, we developed a large-scale, biophysically, and geometrically realistic model of the mouse olfactory bulb and the gamma frequency oscillations[1] it exhibits. Model code and documentation are available at olfactorybulb.org.

The model consists of realistic mitral, tufted (excitatory), and granule (inhibitory) cell models whose electrophysiology and reconstructed morphology have been validated against experimental data using a suite of NeuronUnit[2] validation tests. The cell models were realistically placed, oriented, and confined within anatomically correct mouse olfactory bulb layers obtained from the Allen Brain Atlas[3] using features of BlenderNEURON software[4]. Dendritic proximity was used to form chemical and electrical synapses between principal and inhibitory cell dendrites. Glomeruli were stimulated using simulated odors obtained from optical imaging experiments. The local field potentials generated by the network were monitored and processed using wavelet analysis to replicate a gamma frequency pattern (fingerprint) consisting of an early-high, and later-low frequency temporal components. Simulations were performed using parallel-NEURON[5].

The network was subjected to computational manipulations, which revealed the critical importance of gap junctions, granule cell inhibition, and input strength differences between mitral and tufted cells in generating the gamma fingerprint. Specifically, at glomerular level, gap junctions synchronize the firing of mitral cell and tufted cell populations. Synchronized tufted cells activate granule cells, which inhibit mitral cells. Meanwhile, reduced afferent excitatory input results in mitral cell activation delay, which is amplified by tufted cell activated granule cell inhibition. The interaction between these three mechanisms results two clusters of activity seen in the gamma fingerprint (Fig 1).

The results of the computational experiments support mechanistic hypotheses proposed in earlier experimental work and provide novel insights into the mechanisms responsible for olfactory bulb gamma fingerprint generation, which can be directly tested using common experimental preparations.

Acknowledgments

This work was funded in part by the National Institutes of Health through 1F31DC016811 to JB, R01MH1006674 to SMC, and R01EB021711 to RCG.

References

1. Manabe H, Mori K. Sniff rhythm-paced fast and slow gamma-oscillations in the olfactory bulb: Relation to tufted and mitral cells and behavioral states. J. Neurophysiol. 2013, 110(7), 1593–1599.
2. Gerkin R, Birgiolas J, Jarvis R, et al. NeuronUnit: A package for data-driven validation of neuron models using SciUnit. BioRxiv. 2019, 665331.
3. Oh S, Harris J, Ng L, et al. A mesoscale connectome of the mouse brain. Nature. 2014, 508(7495), 207–214.
4. Birgiolas J. Towards Brains in the Cloud: A Biophysically Realistic Computational Model of Olfactory Bulb. Arizona State University. 2019.
5. Hines M, Carnevale N. The NEURON Simulation Environment. Neural Comput. 1997, 9(6), 1179–1209.

Speakers
avatar for Justas Birgiolas, Ph.D.

Justas Birgiolas, Ph.D.

Research Scholar, Ronin Institue
Primarily interested in building progressively complex biophysically realistic models of neural systems and developing software tools to facilitate model development.


Poster pdf

Monday July 20, 2020 8:00pm - 9:00pm CEST
Slot 05