Expanding evolutionary neuroscience: insights from comparing variation in behavior

Neuroscientists have long studied species with convenient biological features to discover how behavior emerges from conserved molecular, neural, and circuit level processes. With the advent of new tools, viral vectors gene editing automated behavioral analyses, there has been a recent wave interest in developing new, “nontraditional” model species. Here, we advocate for complementary approach development, that is, clade as way integrate an evolutionary comparative neurobiological experiments. Capitalizing on natural variation investing experimental tools clades will be valuable strategy next generation neuroscience discovery. biologists shared animal (Darwin, 1897Darwin C. The Expression Emotions Man Animals. D. Appleton Company, 1897Google Scholar). For much histories their respective fields, however, they pursued this using different research strategies. On one hand, neuroscientists focused questions about molecular neural mechanisms controlled experiments single (i.e., “model” species) chosen or features. By contrast, diversification by comparing multiple share common ancestor clade) because vary behavior. These distinct approaches are own merits, but each also its limitations. While manipulative led fundamental discoveries behavior, limited ability test if those contribute between species, part due relatively infrequent application methods commonly used biologists. Conversely, comparisons provided insight into ultimate causes constraints diversity, it is often challenging hypotheses cellular underpinnings lack very modern research. complementarity these limitations suggests gained program integrates experimentation within quantitative (Figure 1). Such long-standing goal many neuroscientists, particular neuroethologists, who decades championed understanding both proximate (mechanistic) (evolutionary) But achieving requires taking two difficult steps. first develop differ second incorporate generate historical differences In just last few years, made hard-won progress toward steps, barriers falling (from traditional such pharmacology electrophysiological stimulation more optogenetics, vectors, CRISPR-Cas9 genome editing) spread Even task turning continues at increasingly rapid pace, studies explicitly remain rare. discuss interface biology promote integration. Specifically, argue choose study nontraditional systems, should consider not only make especially exciting groups (or clades) which belong phylogenetic exciting. We refer systems balance “model clades” (as contrast species”) suggest capitalize insights nervous system now unprecedented options when deciding underlying mechanisms. This therefore important time think carefully merits chosen. Using relationships help inform choices close integration approaches. Below, summarize motivations present particularly timely discovery, tradeoffs interests might face choosing study, outline well poised answer, some unique challenges implementing clade-based approach. Finally, describe three examples feedback serve inspiration. early history neuroscience, researchers started careers defining interested them then seeking out could most easily answered (Shepherd, 2010Shepherd G. Creating Modern Neuroscience: Revolutionary 1960s. Oxford University Press, 2010Google Scholar, Shepherd, 2016Shepherd Foundations Neuron Doctrine. 2016Google possible almost any question, organism whose conveniently even uniquely suited answering it, observation famously Danish physiologist August Krogh (Krogh, 1929Krogh A. 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More generally, had far longer than laboratory experiment “sample” solutions regulating contexts, permits address extent repertoires promoted constrained question Studying thus contributions offer our evolves shape repertoires. best differences? remains (see Gallant O’Connell, 2020Gallant O’Connell convergent relate genotype phenotype.J. Exp. 223: jeb213447Crossref Scholar notable exceptions), (Donoghue Edwards, 2019Donoghue M.J. E.J. Model vital ascertainment problem practice: response Beaulieu O’Meara (2018).Am. Bot. 106: 327-330Crossref ecology (Cavender-Bares, 2019Cavender-Bares Diversification, adaptation, assembly American oaks (Quercus), integrating evolution.New Phytol. 221: 669-692Crossref (41) and, increasingly, (Church Scholar): clades. Loosely defined, group all members related ancestor. Thus, populations individuals, subspecies, (most commonly) individuals grandparents genera reproductively isolated millions 2). Treating units opposed makes causes. promotes provide key mechanistic basis, evolution. system, no “perfect,” clade-centric applies effectively does individual species; benefit comparisons, probably question. term vague (Katz, 2016bKatz ‘Model organisms’ light evolution.Curr. 26: R649-R650Abstract Marder, 2020bMarder Words without meaning.eLife. 9: e54867Crossref (2) find useful draw parallel widely focal biology) addressing well-defined 3). guiding choice considerations: first, characteristics well-powered methods; second, feasible perform Two requirements well-established manner trait (be molecule) varies relative relationships. clade, power to, reconstruct ancestral states correlations (but, note work experiments). motivate search causes; allows polarize branch change occurred); addition behaviors) likely occurred ancestors present-day correlate environmental variables. seven deer mice methods, generalized least-squares, revealed nesting among closely effect body size climate (Lewarch Hoekstra, 2018Lewarch Hoekstra H.E. 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