Interview with Paul E. Turner of Yale University, who studies the evolutionary genetics of microbes.

Comment on Curr Biol. 2022 Oct 10;32(19):4264-4269.e3.

Comment on Curr Biol. 2022 Nov 7;32(21):4631-4644.e5.

Development is a highly dynamic process in which organisms often experience changes in both form and behavior, which are typically coupled to each other. However, little is known about how organismal-scale behaviors such as body contractility and motility impact morphogenesis. Here, we use the cnidarian Nematostella vectensis as a developmental model to uncover a mechanistic link between organismal size, shape, and behavior. Using quantitative live imaging in a large population of developing animals, combined with molecular and biophysical experiments, we demonstrate that the muscular-hydraulic machinery that controls body movement also drives larva-polyp morphogenesis. We show that organismal size largely depends on cavity inflation through fluid uptake, whereas body shape is constrained by the organization of the muscular system. The generation of ethograms identifies different trajectories of size and shape development in sessile and motile animals, which display distinct patterns of body contractions. With a simple theoretical model, we conceptualize how pressures generated by muscular hydraulics can act as a global mechanical regulator that coordinates tissue remodeling. Altogether, our findings illustrate how organismal contractility and motility behaviors can influence morphogenesis.

Comment on Curr Biol. 2022 Nov 7;32(21):4675-4687.e5.

Comment on Curr Biol. 2022 Nov 7;32(21):4576-4592.e5.

Comment on Curr Biol. 2022 Nov 7;32(21):4620-4630.e5.

Comment on Curr Biol. 2022 Nov 7;32(21):4752-4761.e10.

During development, animals can maintain behavioral output even as underlying circuitry structurally remodels. After hatching, C. elegans undergoes substantial motor neuron expansion and synapse rewiring while the animal continuously moves with an undulatory pattern. To understand how the circuit transitions from its juvenile to mature configuration without interrupting functional output, we reconstructed the C. elegans motor circuit by electron microscopy across larval development. We observed the following: First, embryonic motor neurons transiently interact with the developing post-embryonic motor neurons prior to remodeling of their juvenile wiring. Second, post-embryonic neurons initiate synapse development with their future partners as their neurites navigate through the juvenile nerve cords. Third, embryonic and post-embryonic neurons sequentially build structural machinery needed for the adult circuit before the embryonic neurons relinquish their roles to post-embryonic neurons. Fourth, this transition is repeated region by region along the body in an anterior-to-posterior sequence, following the birth order of neurons. Through this orchestrated and programmed rewiring, the motor circuit gradually transforms from asymmetric to symmetric wiring. These maturation strategies support the continuous maintenance of motor patterns as the juvenile circuit develops into the adult configuration.

Comment in Curr Biol. 2022 Nov 21;32(22):R1279-R1281.

Comment on Curr Biol. 2022 Nov 7;32(21):4719-4726.e4.

Plant leaves display tremendous variation in shape. Here, we discuss how information obtained from genetics, live imaging and computational modeling has helped conceptualize the ways in which gene activity is translated into different leaf shapes. In this framework, the action of genes on leaf form can be captured as the sum of their effects on the amount, duration, and direction of cellular growth, which together produce leaf geometry. We use three different examples to illustrate this point. First, the emergence of complex versus simple leaves in eudicots, which arises from differences in organ-wide growth duration as well as local growth repression at the leaf margin. Second, the development of strap-shaped grass leaves with a broad sheathing base versus the typical eudicot leaves with a narrow petiole, where these features of grass leaves emerged through lateral expansion of the zone of leaf progenitor cells, coupled with later remodeling of growth of early domains of the leaf blade. Third, the formation of insect traps on carnivorous plants that arose through constrained directional growth that produced a 3D deformation. In all the above examples, changes in gene expression of different classes of homeobox genes have contributed to the altered growth patterns underlying these different aspects of leaf shape diversity.

Comment in Curr Biol. 2022 Nov 7;32(21):R1231-R1233.

Microtubules are cytoskeletal polymers that separate chromosomes during mitosis and serve as rails for intracellular transport and organelle positioning. Manipulation of microtubules is widely used in cell and developmental biology, but tools for precise subcellular spatiotemporal control of microtubules are currently lacking. Here, we describe a light-activated system for localized recruitment of the microtubule-severing enzyme katanin. This system, named opto-katanin, uses targeted illumination with blue light to induce rapid, localized, and reversible microtubule depolymerization. This tool allows precise clearing of a subcellular region of microtubules while preserving the rest of the microtubule network, demonstrating that regulation of katanin recruitment to microtubules is sufficient to control its severing activity. The tool is not toxic in the absence of blue light and can be used to disassemble both dynamic and stable microtubules in primary neurons as well as in dividing cells. We show that opto-katanin can be used to locally block vesicle transport and to clarify the dependence of organelle morphology and dynamics on microtubules. Specifically, our data indicate that microtubules are not required for the maintenance of the Golgi stacks or the tubules of the endoplasmic reticulum but are needed for the formation of new membrane tubules. Finally, we demonstrate that this tool can be applied to study the contribution of microtubules to cell mechanics by showing that microtubule bundles can exert forces constricting the nucleus.

Aggression is an adaptive set of behaviors that allows animals to compete against one another in an environment of limited resources. Typically, males fight for mates and food, whereas females fight for food and nest sites.1 Although the study of male aggression has been facilitated by the extravagant nature of the ritualized displays involved and the remarkable armaments sported by males of many species,2,3,4 the subtler and rarer instances of inter-female aggression have historically received much less attention. In Drosophila, females display high levels of complex and highly structured aggression on a food patch with conspecific females.5,6,7,8,9 Other contexts of female aggression have not been explored. Indeed, whether females compete for mating partners, as males do, has remained unknown so far. In the present work, we report that Drosophila melanogaster females reliably display aggression toward mating pairs. This aggressive behavior is regulated by mating status and perception of mating opportunities and relies heavily on olfaction. Furthermore, we found that food odor in combination with OR47b-dependent fly odor sensing is required for proper expression of aggressive behavior. Taken together, we describe a social context linked to reproduction in which Drosophila females aspiring to mate produce consistent and stereotyped displays of aggression. These findings open the door for further inquiries into the neural mechanisms that govern this behavior.

The Vanuatu archipelago served as a gateway to Remote Oceania during one of the most extensive human migrations to uninhabited lands ∼3,000 years ago. Ancient DNA studies suggest an initial settlement by East Asian-related peoples that was quickly followed by the arrival of Papuan-related populations, leading to a major population turnover. Yet there is uncertainty over the population processes and the sociocultural factors that have shaped the genomic diversity of ni-Vanuatu, who present nowadays among the world's highest linguistic and cultural diversity. Here, we report new genome-wide data for 1,433 contemporary ni-Vanuatu from 29 different islands, including 287 couples. We find that ni-Vanuatu derive their East Asian- and Papuan-related ancestry from the same source populations and descend from relatively synchronous, sex-biased admixture events that occurred ∼1,700-2,300 years ago, indicating a peopling history common to the whole archipelago. However, East Asian-related ancestry proportions differ markedly across islands, suggesting that the Papuan-related population turnover was geographically uneven. Furthermore, we detect Polynesian ancestry arriving ∼600-1,000 years ago to Central and South Vanuatu in both Polynesian-speaking and non-Polynesian-speaking populations. Last, we provide evidence for a tendency of spouses to carry similar genetic ancestry, when accounting for relatedness avoidance. The signal is not driven by strong genetic effects of specific loci or trait-associated variants, suggesting that it results instead from social assortative mating. Altogether, our findings provide an insight into both the genetic history of ni-Vanuatu populations and how sociocultural processes have shaped the diversity of their genomes.

Comment in Curr Biol. 2022 Nov 21;32(22):R1281-R1283.

Animals, fungi, and their closest protist relatives comprise the clade Opisthokonta. Although they are comparatively closely related, animals and fungi have diverged greatly from one another. A new study demonstrates that the genomic features that are characteristic of animals and fungi arose even before the origin of these two kingdoms.

Human populations have been shaped by catastrophes that may have left long-lasting signatures in their genomes. One notable example is the second plague pandemic that entered Europe in ca. 1,347 CE and repeatedly returned for over 300 years, with typical village and town mortality estimated at 10%-40%.1 It is assumed that this high mortality affected the gene pools of these populations. First, local population crashes reduced genetic diversity. Second, a change in frequency is expected for sequence variants that may have affected survival or susceptibility to the etiologic agent (Yersinia pestis).2 Third, mass mortality might alter the local gene pools through its impact on subsequent migration patterns. We explored these factors using the Norwegian city of Trondheim as a model, by sequencing 54 genomes spanning three time periods: (1) prior to the plague striking Trondheim in 1,349 CE, (2) the 17th-19th century, and (3) the present. We find that the pandemic period shaped the gene pool by reducing long distance immigration, in particular from the British Isles, and inducing a bottleneck that reduced genetic diversity. Although we also observe an excess of large FST values at multiple loci in the genome, these are shaped by reference biases introduced by mapping our relatively low genome coverage degraded DNA to the reference genome. This implies that attempts to detect selection using ancient DNA (aDNA) datasets that vary by read length and depth of sequencing coverage may be particularly challenging until methods have been developed to account for the impact of differential reference bias on test statistics.

Angiosperm flowers and their animal visitors have co-evolved for at least 140 Ma, and early flowers were likely used mainly as mating and feeding sites by several groups of insects, including beetles, flies, true bugs, and thrips. Earlier studies suggested that shifts from such neutral or antagonistic relationships toward mutualistic pollination interactions between flowers and insects occurred repeatedly during angiosperm evolution. However, the evolutionary mechanisms and adaptations, which accompanied shifts toward effective pollination, are barely understood, and evidence for such scenarios has been lacking. Here, we show that Syngonium hastiferum (Araceae), a Neotropical representative of an otherwise beetle-pollinated clade, is pollinated by plant bugs (Miridae; Heteroptera), which are florivores of Syngonium schottianum and other Araceae species. We found that S. hastiferum differs in several floral traits from its beetle-pollinated relatives. Scent emission and thermogenesis occur in the morning instead of the evening hours, and its pollen surface is spiny instead of smooth. Furthermore, the floral scent of S. hastiferum includes a previously unknown natural product, (Z)-3-isopropylpent-3-en-1-ol, which we show to have a function in specifically attracting the plant bug pollinators. This is the first known case of a specialized plant bug pollination system and provides clear evidence for the hypothesis that the adoption of antagonistic florivores as pollinators can drive flower diversification. VIDEO ABSTRACT.

Does low frequency sound (bass) make people dance more? Music that makes people want to move tends to have more low frequency sound, and bass instruments typically provide the musical pulse that people dance to1. Low pitches confer advantages in perception and movement timing, and elicit stronger neural responses for timing compared to high pitches2, suggesting superior sensorimotor communication. Low frequency sound is processed via vibrotactile3 and vestibular4 (in addition to auditory) pathways, and stimulation of these non-auditory modalities in the context of music can increase ratings of groove (the pleasurable urge to move to music)3, and modulate musical rhythm perception4. Anecdotal accounts describe intense physical and psychological effects of low frequencies, especially in electronic dance music5, possibly reflecting effects on physiological arousal. We do not, however, know if these associations extend to direct causal effects of low frequencies in complex, real-world, social contexts like dancing at concerts, or if low frequencies that are not consciously detectable can affect behaviour. We tested whether non-auditory low-frequency stimulation would increase audience dancing by turning very-low frequency (VLF) speakers on and off during a live electronic music concert and measuring audience members' movements using motion-capture. Movement increased when VLFs were present, and because the VLFs were below or near auditory thresholds (and a subsequent experiment suggested they were undetectable), we believe this represents an unconscious effect on behaviour, possibly via vestibular and/or tactile processing.

Comment in Curr Biol. 2022 Nov 7;32(21):R1237-R1240.

Erratum in Curr Biol. 2022 Nov 7;32(21):4780-4781.

Comment in Curr Biol. 2022 Nov 7;32(21):R1226-R1228.

Loss of appetite and negative energy balance are common features of endotoxemia in all animals and are thought to have protective roles by reducing nutrient availability to host and pathogen metabolism. Accordingly, fasting and caloric restriction have well-established anti-inflammatory properties. However, in response to reduced nutrient availability at the cellular and organ levels, negative energy balance also recruits distinct energy-sensing brain circuits, but it is not known whether these neuronal systems have a role in its anti-inflammatory effects. Here, we report that hypothalamic AgRP neurons-a critical neuronal population for the central representation of negative energy balance-have parallel immunoregulatory functions. We found that when endotoxemia occurs in fasted mice, the activity of AgRP neurons remains sustained, but this activity does not influence feeding behavior and endotoxemic anorexia. Furthermore, we found that endotoxemia acutely desensitizes AgRP neurons, which also become refractory to inhibitory signals. Mimicking this sustained AgRP neuron activity in fed mice by chemogenetic activation-a manipulation known to recapitulate core behavioral features of fasting-results in reduced acute tumor necrosis factor alpha (TNF-α) release during endotoxemia. Mechanistically, we found that endogenous glucocorticoids play an important role: glucocorticoid receptor deletion from AgRP neurons prevents their endotoxemia-induced desensitization, and importantly, it counteracts the fasting-induced suppression of TNF-α release, resulting in prolonged sickness. Together, these findings provide evidence directly linking AgRP neuron activity to the acute response during endotoxemia, suggesting that these neurons are a functional component of the immunoregulatory effects associated with negative energy balance and catabolic metabolism.

Among extant animals, Lophotrochozoa accounts for the majority of phyla.1 This bilaterian clade radiated rapidly during the Cambrian explosion, obfuscating its phylogenetic relationships and rendering many aspects of its early evolution uncertain. Many early lophotrochozoans are known only from isolated skeletal microfossils, "small shelly fossils," often derived from larger animals with complex multi-element skeletons.2 The discovery of articulated fossils has revealed surprising insights into the animals from which these skeletal pieces were derived, such as paired shells in the mollusc Halkieria.3 Tommotiids are a key group of phosphatic early skeletal fossils that first appear in the late early Cambrian.4,5 Although their affinities were previously obscure, discoveries of partial scleritomes and investigations of growth and microstructure6 provide links with Brachiopoda7,8 and Phoronida,9 two of the lophophorate phyla. By contrast, the body plan of camenellan tommotiids remains a palaeontological mystery, with hypothetical reconstructions representing motile, benthic, dorsally armored worms.4,10 Here, we describe an articulated camenellan (Wufengella bengtsoni gen. et sp. nov.) from the Cambrian Chengjiang Biota, China, revealing the morphology of the scleritome and the first soft tissues from an adult tommotiid. Wufengella carries two dorsal rows of sclerites in a highly asymmetric arrangement, flanked by smaller, cap-shaped sclerites. The scleritome was fringed by iterated fascicles of chaetae and two layers of flattened lobes. Phylogenetic analysis confirms that camenellans occupy a deep branch in lophophorate phylogeny, prior to the acquisition of a sessile lifestyle. Wufengella reveals direct evidence for a metameric body plan reminiscent of annelids early in the evolutionary history of lophophorates.11,12.

Comment in Curr Biol. 2022 Nov 7;32(21):R1235-R1237.

Over the past decade, molecular phylogenetics has reshaped our understanding of the fungal tree of life by unraveling a hitherto elusive diversity of the protistan relatives of Fungi. Aphelida constitutes one of these novel deep branches that precede the emergence of osmotrophic fungal lifestyle and hold particular significance as the pathogens of algae. Here, we obtain and analyze the genomes of aphelid species Amoeboaphelidium protococcarum and Amoeboaphelidium occidentale. Genomic data unmask the vast divergence between these species, hidden behind their morphological similarity, and reveal hybrid genomes with a complex evolutionary history in two strains of A. protococcarum. We confirm the proposed sister relationship between Aphelida and Fungi using phylogenomic analysis and chart the reduction of characteristic proteins involved in phagocytic activity in the evolution of Holomycota. Annotation of aphelid genomes demonstrates the retention of actin nucleation-promoting complexes associated with phagocytosis and amoeboid motility and also reveals a conspicuous expansion of receptor-like protein kinases, uncharacteristic of fungal lineages. We find that aphelids possess multiple carbohydrate-processing enzymes that are involved in fungal cell wall synthesis but do not display rich complements of algal cell-wall-processing enzymes, suggesting an independent origin of fungal plant-degrading capabilities. Aphelid genomes show that the emergence of Fungi from phagotrophic ancestors relied on a common cell wall synthetic machinery but required a different set of proteins for digestion and interaction with the environment.

Urban environments are high risk areas for large carnivores, where anthropogenic disturbances can reduce fitness and increase mortality risk.1 When catastrophic events like large wildfires occur, trade-offs between acquiring resources and avoiding risks of the urban environment are intensified. This landscape context could lead to an increase in risk-taking behavior by carnivores if burned areas do not allow them to meet their energetic needs, potentially leading to human-wildlife conflict.2,3 We studied mountain lion behavior using GPS location and accelerometer data from 17 individuals tracked before and after a large wildfire (the 2018 Woolsey Fire) within a highly urbanized area (Los Angeles, California, USA). After the wildfire, mountain lions avoided burned areas and increased behaviors associated with anthropogenic risk, including more frequent road and freeway crossings (mean crossings increased from 3 to 5 per month) and greater activity during the daytime (means from increased 10% to 16% of daytime active), a time when they are most likely to encounter humans. Mountain lions also increased their amount of space used, distance traveled (mean distances increased from 250 to 390 km per month), and intrasexual overlap, potentially putting them at risk of intraspecific conflict. Joint pressures from urbanization and severe wildfire, alongside resulting risk-taking, could thus increase mortality and extinction risk for populations already suffering from low genetic diversity, necessitating increased connectivity in fire-prone areas.

The Golgi is the central sorting station in the secretory pathway and thus the destination of transport vesicles arriving from the endoplasmic reticulum and endosomes and from within the Golgi itself. Cell viability, therefore, requires that the Golgi accurately receives multiple classes of vesicle. One set of proteins proposed to direct vesicle arrival at the Golgi are the golgins, long coiled-coil proteins localized to specific parts of the Golgi stack. In mammalian cells, three of the golgins, TMF, golgin-84, and GMAP-210, can capture intra-Golgi transport vesicles when placed in an ectopic location. However, the individual golgins are not required for cell viability, and mouse knockout mutants only have defects in specific tissues. To further illuminate this system, we examine the Drosophila orthologs of these three intra-Golgi golgins. We show that ectopic forms can capture intra-Golgi transport vesicles, but strikingly, the cargo present in the vesicles captured by each golgin varies between tissues. Loss-of-function mutants show that the golgins are individually dispensable, although the loss of TMF recapitulates the male fertility defects observed in mice. However, the deletion of multiple golgins results in defects in glycosylation and loss of viability. Examining the vesicles captured by a particular golgin when another golgin is missing reveals that the vesicle content in one tissue changes to resemble that of a different tissue. This reveals a plasticity in Golgi organization between tissues, providing an explanation for why the Golgi is sufficiently robust to tolerate the loss of many of the individual components of its membrane traffic machinery.

Comment in Curr Biol. 2022 Nov 7;32(21):R1228-R1231.

Comment in Curr Biol. 2022 Nov 7;32(21):R1233-R1235.

Walking - humans' most fundamental form of moderate intensity physical activity - is associated with reduced risks of morbidity and mortality. Evolutionary perspectives have contributed much to understanding the effects of walking and other physical activities on health; however, we know comparatively little about how step counts (steps taken per day) changed over the course of human evolution, potentially affecting how selection operated on physiological responses to moderate intensity physical activity that influence morbidity and mortality. Here, we compare step counts across humans and our closest living relatives, the great apes. Compiling data from epidemiology and comparative physiology, we show how step counts more than tripled during human evolution, potentially linking higher levels of moderate intensity physical activity with reduced morbidity and mortality, and we highlight how recent decreases in step counts are an evolutionary mismatch. We raise the hypothesis that the dose-response relationship between moderate intensity physical activity and health was shifted in humans to require more steps per day to promote extended healthspan and lifespan.

Emilie Didaskalou and colleagues introduce the analysis of DNA form environmental samples.

Interview with Thomas Collett, Emeritus Professor at the University of Sussex, who has spent many decades studying insect navigation.

Structures created by animals can serve many purposes. Spiders weave intricate webs to trap prey; beavers engineer complex networks of dams to alter waterways; male bower birds construct and decorate elaborate bowers to attract mates. Animal architecture ranges widely in function, but by far the most common use is shelter. Animals can spend a large amount of time in their shelters, and this is often where they both sleep and rear young, two of the most vulnerable states in animal lives. To optimize the safety and suitability of refuges available to them, many animals have become architects and create their own shelters, ranging from simple holes in the ground to the large complex nests of some social insects.

Comment on Curr Biol. 2022 Nov 21;32(22):4941-4948.e3.

Comment on Curr Biol. 2022 Nov 21;32(22):4949-4956.e3.

Comment on Curr Biol. 2022 Nov 21;32(22):4881-4889.e5.

Comment in Curr Biol. 2022 Nov 21;32(22):R1264-R1266.

Comment on Curr Biol. 2022 Nov 21;32(22):4783-4796.e3.

How gene activities and biomechanics together direct organ shapes is poorly understood. Plant leaf and floral organs develop from highly similar initial structures and share similar gene expression patterns, yet they gain drastically different shapes later-flat and bilateral leaf primordia and radially symmetric floral primordia, respectively. We analyzed cellular growth patterns and gene expression in young leaves and flowers of Arabidopsis thaliana and found significant differences in cell growth rates, which correlate with convergence sites of phytohormone auxin that require polar auxin transport. In leaf primordia, the PRESSED-FLOWER-expressing middle domain grows faster than adjacent adaxial domain and coincides with auxin convergence. In contrast, in floral primordia, the LEAFY-expressing domain shows accelerated growth rates and pronounced auxin convergence. This distinct cell growth dynamics between leaf and flower requires changes in levels of cell-wall pectin de-methyl-esterification and mechanical properties of the cell wall. Data-driven computer model simulations at organ and cellular levels demonstrate that growth differences are central to obtaining distinct organ shape, corroborating in planta observations. Together, our study provides a mechanistic basis for the establishment of early aerial organ symmetries through local modulation of differential growth patterns with auxin and biomechanics.

Comment on Curr Biol. 2022 Nov 21;32(22):4975-4981.e3.

Food handling offers unique yet largely unexplored opportunities to investigate how cortical activity relates to forelimb movements in a natural, ethologically essential, and kinematically rich form of manual dexterity. To determine these relationships, we recorded high-speed (1,000 fps) video and multi-channel electrophysiological cortical spiking activity while mice handled food. The high temporal resolution of the video allowed us to decompose active manipulation ("oromanual") events into characteristic submovements, enabling event-aligned analysis of cortical activity. Activity in forelimb M1 was strongly modulated during food handling, generally higher during oromanual events and lower during holding intervals. Optogenetic silencing and stimulation of forelimb M1 neurons partially affected food-handling movements, exerting suppressive and activating effects, respectively. We also extended the analysis to forelimb S1 and lateral M1, finding broadly similar oromanual-related activity across all three areas. However, each area's activity displayed a distinct timing and phasic/tonic temporal profile, which was further analyzed by non-negative matrix factorization and demonstrated to be attributable to area-specific composition of activity classes. Current or future forelimb position could be accurately predicted from activity in all three regions, indicating that the cortical activity in these areas contains high information content about forelimb movements during food handling. These results thus establish that cortical activity during food handling is manipulation specific, distributed, and broadly similar across multiple sensorimotor areas while also exhibiting area- and submovement-specific relationships with the fast kinematic hallmarks of this natural form of complex free-object-handling manual dexterity.

Comment in Curr Biol. 2022 Nov 21;32(22):R1262-R1264.

Comment on Curr Biol. 2022 Nov 7;32(21):4593-4606.e8.

Comment on Curr Biol. 2022 Nov 7;32(21):R1224-R1225.

Comment on Curr Biol. 2022 Nov 21;32(22):4982-4988.e4.

Comment in Curr Biol. 2022 Nov 21;32(22):R1269-R1271.

Many of the sensations experienced by an organism are caused by their own actions, and accurately anticipating both the sensory features and timing of self-generated stimuli is crucial to a variety of behaviors. In the auditory cortex, neural responses to self-generated sounds exhibit frequency-specific suppression, suggesting that movement-based predictions may be implemented early in sensory processing. However, it remains unknown whether this modulation results from a behaviorally specific and temporally precise prediction, nor is it known whether corresponding expectation signals are present locally in the auditory cortex. To address these questions, we trained mice to expect the precise acoustic outcome of a forelimb movement using a closed-loop sound-generating lever. Dense neuronal recordings in the auditory cortex revealed suppression of responses to self-generated sounds that was specific to the expected acoustic features, to a precise position within the movement, and to the movement that was coupled to sound during training. Prediction-based suppression was concentrated in L2/3 and L5, where deviations from expectation also recruited a population of prediction-error neurons that was otherwise unresponsive. Recording in the absence of sound revealed abundant movement signals in deep layers that were biased toward neurons tuned to the expected sound, as well as expectation signals that were present throughout the cortex and peaked at the time of expected auditory feedback. Together, these findings identify distinct populations of auditory cortical neurons with movement, expectation, and error signals consistent with a learned internal model linking an action to its specific acoustic outcome.

Comment on Curr Biol. 2022 Nov 21;32(22):4989-4996.e3.

Comment in Curr Biol. 2022 Nov 21;32(22):R1283-R1286.

Unique aspects of human behavior are often attributed to differences in the relative size and organization of the human brain: these structural aspects originate during early development. Recent studies indicate that human neurodevelopment is considerably slower than that in other nonhuman primates, a finding that is termed neoteny. One aspect of neoteny is the slow onset of action potentials. However, which molecular mechanisms play a role in this process remain unclear. To examine the evolutionary constraints on the rate of neuronal maturation, we have generated transcriptional data tracking five time points, from the neural progenitor state to 8-week-old neurons, in primates spanning the catarrhine lineage, including Macaca mulatta, Gorilla gorilla, Pan paniscus, Pan troglodytes, and Homo sapiens. Despite finding an overall similarity of many transcriptional signatures, species-specific and clade-specific distinctions were observed. Among the genes that exhibited human-specific regulation, we identified a key pioneer transcription factor, GATA3, that was uniquely upregulated in humans during the neuronal maturation process. We further examined the regulatory nature of GATA3 in human cells and observed that downregulation quickened the speed of developing spontaneous action potentials, thereby modulating the human neotenic phenotype. These results provide evidence for the divergence of gene regulation as a key molecular mechanism underlying human neoteny.

Earth's wilderness areas are reservoirs of genetic information and carbon storage systems, and are vital to reducing extinction risks. Retaining the conservation value of these areas is fundamental to achieving global biodiversity conservation goals; however, climate and land-use risk can undermine their ability to provide these functions. The extent to which wilderness areas are likely to be impacted by these drivers has not previously been quantified. Using climate and land-use change during baseline (1971-2005) and future (2016-2050) periods, we estimate that these stressors within wilderness areas will increase by ca. 60% and 39%, respectively, under a scenario of high emission and land-use change (SSP5-RCP8.5). Nearly half (49%) of all wilderness areas could experience substantial climate change by 2050 under this scenario, potentially limiting their capacity to shelter biodiversity. Notable climate (>5 km year-1) and land-use (>0.25 km year-1) changes are expected to occur more rapidly in the unprotected wilderness, including the edges of the Amazonian wilderness, Northern Russia, and Central Africa, which support unique assemblages of species and are critical for the preservation of biodiversity. However, an alternative scenario of sustainable development (SSP1-RCP2.6) would attenuate the projected climate velocity and land-use instability by 54% and 6%, respectively. Mitigating greenhouse gas emissions and preserving the remaining intact natural ecosystems can help fortify these bastions of biodiversity.

Comment on Nature. 2022 Sep;609(7929):986-993.

Nightmare disorder (ND) is characterized by dreams with strong negative emotions occurring during rapid eye movement (REM) sleep. ND is mainly treated by imagery rehearsal therapy (IRT), where the patients are asked to change the negative story line of their nightmare to a more positive one. We here used targeted memory reactivation (TMR) during REM sleep to strengthen IRT-related memories and accelerate remission of ND. Thirty-six patients with ND were asked to perform an initial IRT session and, while they generated a positive outcome of their nightmare, half of the patients were exposed to a sound (TMR group), while no such pairing took place for the other half (control group). During the next 2 weeks, all patients performed IRT every evening at home and were exposed to the sound during REM sleep with a wireless headband, which automatically detected sleep stages. The frequency of nightmares per week at 2 weeks was used as the primary outcome measure. We found that the TMR group had less frequent nightmares and more positive dream emotions than the control group after 2 weeks of IRT and a sustained decrease of nightmares after 3 months. By demonstrating the effectiveness of TMR during sleep to potentiate therapy, these results have clinical implications for the management of ND, with relevance to other psychiatric disorders too. Additionally, these findings show that TMR applied during REM sleep can modulate emotions in dreams.

Elasmobranchs (sharks, rays, and skates) are caught throughout fisheries globally, leading to over one-third of species being threatened with extinction1. Oceanic shark populations have undergone an average 71% decline over the last half century, owing to an 18-fold increase in relative fishing pressure2. Incidental capture or 'bycatch' is a primary driver of population declines, and poses an important challenge for species conservation3. This threat necessitates mitigation strategies that exist for sharks but are often focussed on haul-back and post-capture effects for longline fishing. We trialled a novel shark bycatch mitigation device ("SharkGuard") in a commercial longline fishery targeting bluefin tuna (Thunnus thynnus), where bycatch consists largely of blue sharks (Prionace glauca) and pelagic stingrays (Pteroplatytrygon violacea).

Comment in Curr Biol. 2022 Nov 21;32(22):R1276-R1278.

Elucidating how the distinct components of synaptic plasticity dynamically orchestrate the distinct stages of memory acquisition and maintenance within neuronal networks remains a major challenge. Specifically, plasticity processes tuning the functional and also structural state of presynaptic active zone (AZ) release sites are widely observed in vertebrates and invertebrates, but their behavioral relevance remains mostly unclear. We here provide evidence that a transient upregulation of presynaptic AZ release site proteins supports aversive olfactory mid-term memory in the Drosophila mushroom body (MB). Upon paired aversive olfactory conditioning, AZ protein levels (ELKS-family BRP/(m)unc13-family release factor Unc13A) increased for a few hours with MB-lobe-specific dynamics. Kenyon cell (KC, intrinsic MB neurons)-specific knockdown (KD) of BRP did not affect aversive olfactory short-term memory (STM) but strongly suppressed aversive mid-term memory (MTM). Different proteins crucial for the transport of AZ biosynthetic precursors (transport adaptor Aplip1/Jip-1; kinesin motor IMAC/Unc104; small GTPase Arl8) were also specifically required for the formation of aversive olfactory MTM. Consistent with the merely transitory increase of AZ proteins, BRP KD did not interfere with the formation of aversive olfactory long-term memory (LTM; i.e., 1 day). Our data suggest that the remodeling of presynaptic AZ refines the MB circuitry after paired aversive conditioning, over a time window of a few hours, to display aversive olfactory memories.

Comment in Curr Biol. 2022 Nov 21;32(22):R1267-R1269.

Comment in Curr Biol. 2022 Nov 21;32(22):R1274-R1276.

How the homeostatic drive for sleep accumulates over time and is released remains poorly understood. In Drosophila, we previously identified the R5 ellipsoid body (EB) neurons as putative sleep drive neurons1 and recently described a mechanism by which astrocytes signal to these cells to convey sleep need.2 Here, we examine the mechanisms acting downstream of the R5 neurons to promote sleep. EM connectome data demonstrate that R5 neurons project to EPG neurons.3 Broad thermogenetic activation of EPG neurons promotes sleep, whereas inhibiting these cells reduces homeostatic sleep rebound. Perforated patch-clamp recordings reveal that EPG neurons exhibit elevated spontaneous firing following sleep deprivation, which likely depends on an increase in extrinsic excitatory inputs. Our data suggest that cholinergic R5 neurons participate in the homeostatic regulation of sleep, and epistasis experiments indicate that the R5 neurons act upstream of EPG neurons to promote sleep. Finally, we show that the physical and functional connectivity between the R5 and EPG neurons increases with greater sleep need. Importantly, dual patch-clamp recordings demonstrate that activating R5 neurons induces cholinergic-dependent excitatory postsynaptic responses in EPG neurons. Moreover, sleep loss triggers an increase in the amplitude of these responses, as well as in the proportion of EPG neurons that respond. Together, our data support a model whereby sleep drive strengthens the functional connectivity between R5 and EPG neurons, triggering sleep when a sufficient number of EPG neurons are activated. This process could enable the proper timing of the accumulation and release of sleep drive.

Many plant cells exhibit polarity, revealed by asymmetric localization of specific proteins within each cell.1,2,3,4,5,6 Polarity is typically coordinated between cells across a tissue, raising the question of how coordination is achieved. One hypothesis is that mechanical stresses provide cues.7 This idea gains support from experiments in which cotyledons were mechanically stretched transversely to their midline.8 These previously published results showed that without applied tension, the stomatal lineage cell polarity marker, BREVIS RADIX-LIKE 2 (BRXL2), exhibited no significant excess in the transverse orientation. By contrast, 7 h after stretching, BRXL2 polarity distribution exhibited transverse excess, aligned with the stretch direction. These stretching experiments involved statistical comparisons between snapshots of stretched and unstretched cotyledons, with different specimens being imaged in each case.8 Here, we image the same cotyledon before and after stretching and find no evidence for reorientation of polarity. Instead, statistical analysis shows that cotyledons contain a pre-existing transverse excess in BRXL2 polarity orientation that is not significantly modified by applied tension. The transverse excess reflects BRLX2 being preferentially localized toward the medial side of the cell, nearer to the cotyledon midline, creating a weak medial bias. A second polarity marker, BREAKING OF ASYMMETRY IN THE STOMATAL LINEAGE (BASL), also exhibits weak medial bias in stomatal lineages, whereas ectopic expression of BASL in non-stomatal cells exhibits strong proximal bias, as previously observed in rosette leaves. This proximal bias is also unperturbed by applied tension. Our findings therefore show that cotyledons contain two near-orthogonal coordinated biases in planar polarity: mediolateral and proximodistal.

Comment in Curr Biol. 2022 Dec 5;32(23):R1318-R1320.

Cell migration is crucial for organismal development and shapes organisms in health and disease. Although a lot of research has revealed the role of intracellular components and extracellular signaling in driving single and collective cell migration, the influence of physical properties of the tissue and the environment on migration phenomena in vivo remains less explored. In particular, the role of the extracellular matrix (ECM), which many cells move upon, is currently unclear. To overcome this gap, we use zebrafish optic cup formation, and by combining novel transgenic lines and image analysis pipelines, we study how ECM properties influence cell migration in vivo. We show that collectively migrating rim cells actively move over an immobile extracellular matrix. These cell movements require cryptic lamellipodia that are extended in the direction of migration. Quantitative analysis of matrix properties revealed that the topology of the matrix changes along the migration path. These changes in matrix topologies are accompanied by changes in the dynamics of cell-matrix interactions. Experiments and theoretical modeling suggest that matrix porosity could be linked to efficient migration. Indeed, interfering with matrix topology by increasing its porosity results in a loss of cryptic lamellipodia, less-directed cell-matrix interactions, and overall inefficient migration. Thus, matrix topology is linked to the dynamics of cell-matrix interactions and the efficiency of directed collective rim cell migration during vertebrate optic cup morphogenesis.

Aversive olfactory conditioning in Drosophila is a valuable model for elucidating the mechanism of associative learning. Much effort has centered around the role of neuroplasticity at the mushroom body (MB)-mushroom body output neuron (MBON) synapses in mapping odors to specific behaviors. By electrophysiological recordings from MB neurons, we discovered a form of input-timing-dependent plasticity at the incoming synapses from projection neurons that controls the efficacy of aversive olfactory memory formation. Importantly, this plasticity is facilitated by the neural activity of PPL1, the neuronal cluster that also modulates MB-MBON connections at the output stage of MB. Unlike the MB-MBON synapses that probably utilize dopamine D1-like receptors, this neuroplasticity is dependent on D2-like receptors that are expressed mainly by γ Kenyon cells noticeably in their somato-dendritic region. The D2-like receptors recruit voltage-gated calcium channels, leading to calcium influx in the soma and dendrites of γ neurons. Together, our results reveal a previously unrecognized synaptic component of the MB circuit architecture that not only could increase the salience of a conditioning odor but also couples the process of memory encoding and valency mapping to drive-associative learning.

The role of the gustatory region of the insular cortex in mediating associative taste learning, such as conditioned taste aversion, has been well studied. However, while associative learning plays a role in some taste behaviors, such as avoiding toxins, animals often encounter taste stimuli in their natural environment without explicit consequences. This type of inconsequential experience with sensory stimuli has been studied in other sensory systems, generally with the finding that neuronal responses habituate with repeated sensory exposure. This study sought to determine the effect of taste familiarity on population taste coding in the mouse gustatory cortex (GC). Using microendoscope calcium imaging, we studied the taste responses of visually identifiable neurons over 5 days of taste experience, during which animals could freely choose to consume taste stimuli. We found that the number of active cells in the insular cortex, as well as the number of cells characterized as taste-responsive, significantly decreased as animals became familiar with taste stimuli. Moreover, the magnitude of taste-evoked excited responses increased while inhibited responses decreased with experience. By tracking individual neurons over time, we identified a subpopulation of stable neurons present on all days of the taste familiarity paradigm and further characterized their taste coding properties. The population-level response across these stable cells was distinct for each taste quality when taste stimuli were novel, but population responses for readily consumed stimuli became more correlated as the stimuli became familiar. Overall, these results highlight the effects of familiarity on both taste-specific and non-taste responses in the gustatory cortex.