Probing brains with neuron-inspired electronics

March 4, 2019

Molecular classification of foveal cell types in primate retina

February 21, 2019
Cell. 2019 Jan 28. pii: S0092-8674(19)30037-6. doi: 10.1016/j.cell.2019.01.004. [Epub ahead of print]

Molecular Classification and Comparative Taxonomics of Foveal and Peripheral Cells in Primate Retina.



High-acuity vision in primates, including humans, is mediated by a small central retinal region called the fovea. As more accessible organisms lack a fovea, its specialized function and its dysfunction in ocular diseases remain poorly understood. We used 165,000 single-cell RNA-seq profiles to generate comprehensive cellular taxonomies of macaque fovea and peripheral retina. More than 80% of >60 cell types match between the two regions but exhibit substantial differences in proportions and gene expression, some of which we relate to functional differences. Comparison of macaque retinal types with those of mice reveals that interneuron types are tightly conserved. In contrast, projection neuron types and programs diverge, despite exhibiting conserved transcription factor codes. Key macaque types are conserved in humans, allowing mapping of cell-type and region-specific expression of >190 genes associated with 7 human retinal diseases. Our work provides a framework for comparative single-cell analysis across tissue regions and species.

Linking a mutation to survival in wild mice

February 1, 2019

Barrett RDH, Laurent S, Mallarino R, Pfeifer SP, Xu CCY, Foll M, Wakamatsu K, Duke-Cohan JS, Jensen JD, Hoekstra HE

Adaptive evolution in new or changing environments can be difficult to predict because the functional connections between genotype, phenotype, and fitness are complex. Here, we make these explicit connections by combining field and laboratory experiments in wild mice. We first directly estimate natural selection on pigmentation traits and an underlying pigment locus, Agouti, by using experimental enclosures of mice on different soil colors. Next, we show how a mutation in Agouti associated with survival causes lighter coat color through changes in its protein binding properties. Together, our findings demonstrate how a sequence variant alters phenotype and then reveal the ensuing ecological consequences that drive changes in population allele frequency, thereby illuminating the process of evolution by natural selection.


Nature Method of the Year 2018: Imaging in freely behaving animals

January 30, 2019

Each year, Nature Methods selects a Method of the Year. Past winners have included Organoids, single-cell sequencing, and single-molecule cryo-EM. For 2018, the Method of the Year was Imaging in freely behaving animals. Aravi Samuel's lab was cited, and Aravi and John Calarco wrote an accompanying Comment.

Structured Odorant Response Patterns across a Complete Olfactory Receptor Neuron Population

January 16, 2019

Si G, Kanwal JK, Hu Y, Tabone CJ, Baron J, Berck M1, Vignoud G, Samuel ADT

Odor perception allows animals to distinguish odors, recognize the same odor across concentrations, and determine concentration changes. How the activity patterns of primary olfactory receptor neurons (ORNs), at the individual and population levels, facilitate distinguishing these functions remains poorly understood. Here, we interrogate the complete ORN population of the Drosophila larva across a broadly sampled panel of odorants at varying concentrations. We find that the activity of each ORN scales with the concentration of any odorant via a fixed dose-response function with a variable sensitivity. Sensitivities across odorants and ORNs follow a power-law distribution. Much of receptor sensitivity to odorants is accounted for by a single geometrical property of molecular structure. Similarity in the shape of temporal response filters across odorants and ORNs extend these relationships to fluctuating environments. These results uncover shared individual- and population-level patterns that together lend structure to support odor perceptions.