Computational exploration of molecular receptive fields in the olfactory bulb reveals a glomerulus-centric chemical map

© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Progress in olfactory research is currently hampered by incomplete knowledge about chemical receptive ranges of primary receptors. Moreover, the chemical logic underlying the arrangement of computational units in the olfactory bulb has still not been resolved. We undertook a large-scale approach at characterising molecular receptive ranges (MRRs) of glomeruli in the dorsal olfactory bulb (dOB) innervated by the MOR18-2 olfactory receptor, also known as Olfr78, with human ortholog OR51E2. Guided by an iterative approach that combined biological screening and machine learning, we selected 214 odorants to characterise the response of MOR18-2 and its neighbouring glomeruli. We found that a combination of conventional physico-chemical and vibrational molecular descriptors performed best in predicting glomerular responses using nonlinear Support-Vector Regression. We also discovered several previously unknown odorants activating MOR18-2 glomeruli, and obtained detailed MRRs of MOR18-2 glomeruli and their neighbours. Our results confirm earlier findings that demonstrated tunotopy, that is, glomeruli with similar tuning curves tend to be located in spatial proximity in the dOB. In addition, our results indicate chemotopy, that is, a preference for glomeruli with similar physico-chemical MRR descriptions being located in spatial proximity. Together, these findings suggest the existence of a partial chemical map underlying glomerular arrangement in the dOB. Our methodology that combines machine learning and physiological measurements lights the way towards future high-throughput studies to deorphanise and characterise structure-activity relationships in olfaction.Peer reviewe

A model of fasciculation and sorting in mixed populations of axons

We extend a recently proposed model (Chaudhuri et al., EPL 87, 20003 (2009)) aiming to describe the formation of fascicles of axons during neural development. The growing axons are represented as paths of interacting directed random walkers in two spatial dimensions. To mimic turnover of axons, whole paths are removed and new walkers are injected with specified rates. In the simplest version of the model, we use strongly adhesive short-range inter-axon interactions that are identical for all pairs of axons. We generalize the model to adhesive interactions of finite strengths and to multiple types of axons with type-specific interactions. The dynamic steady state is characterized by the position-dependent distribution of fascicle sizes. With distance in the direction of axon growth, the mean fascicle size and emergent time scales grow monotonically, while the degree of sorting of fascicles by axon type has a maximum at a finite distance. To understand the emergence of slow time scales, we develop an analytical framework to analyze the interaction between neighboring fascicles.Comment: 19 pages, 13 figures; version accepted for publication in Phys Rev

Response Dynamics of Entorhinal Cortex in Awake, Anesthetized, and Bulbotomized Rats. <i>Brain Research</i> <b>911</b>(2)

The generation of oscillatory activity may be crucial to brain function. The coordination of individual neurons into rhythmic and coherently active populations is thought to result from interactions between excitatory and inhibitory cells mediated by local feedback connections. By using extracellular recording wires and silicon microprobes to measure electrically evoked damped oscillatory responses at the level of neural populations in the entorhinal cortex, and by using current-source density analysis to determine the spatial pattern of evoked responses, we show that the propagation of activity through the cortical circuit and consequent oscillations in the local field potential are dependent upon background neural activity. Pharmacological manipulations as well as surgical disconnection of the olfactory bulb serve to quell the background excitatory input incident to entorhinal cortex, resulting in evoked responses without characteristic oscillations and showing no signs of polysynaptic feedback. Electrical stimulation at 200 Hz applied to the lateral olfactory tract provides a substitute for the normal background activity emanating from the bulb and enables the generation of oscillatory responses once again. We conclude that a nonzero background level of activity is necessary and sufficient to sustain normal oscillatory responses and polysynaptic transmission through the entorhinal cortex

Endocranial Morphology of the Extinct North American Lion (Panthera atrox)

The extinct North American lion (Panthera atrox) is one of the largest felids (Mammalia, Carnivora) to have ever lived, and it is known from a plethora of incredibly well-preserved remains. Despite this abundance of material, there has been little research into its endocranial anatomy. CT scans of a skull of P. atrox from the Pleistocene La Brea Tar pits were used to generate the first virtual endocranium for this species and to elucidate previously unknown details of its brain size and gross structure, cranial nerves, and inner-ear morphology. Results show that its gross brain anatomy is broadly similar to that of other pantherines, although P. atrox displays less cephalic flexure than either extant lions or tigers, instead showing a brain shape that is reminiscent of earlier felids. Despite this unusual reduction in flexure, the estimated absolute brain size for this specimen is one of the largest reported for any felid, living or extinct. Its encephalization quotient (brain size as a fraction of the expected brain mass for a given body mass) is also larger than that of extant lions but similar to that of the other pantherines. The advent of CT scans has allowed nondestructive sampling of anatomy that cannot otherwise be studied in these extinct lions, leading to a more accurate reconstruction of endocranial morphology and its evolution

Odors: from chemical structures to gaseous plumes

We are immersed within an odorous sea of chemical currents that we parse into individual odors with complex structures. Odors have been posited as determined by the structural relation between the molecules that compose the chemical compounds and their interactions with the receptor site. But, naturally occurring smells are parsed from gaseous odor plumes. To give a comprehensive account of the nature of odors the chemosciences must account for these large distributed entities as well. We offer a focused review of what is known about the perception of odor plumes for olfactory navigation and tracking, which we then connect to what is known about the role odorants play as properties of the plume in determining odor identity with respect to odor quality. We end by motivating our central claim that more research needs to be conducted on the role that odorants play within the odor plume in determining odor identity