Interview with Lisa Manning, Director of the BioInspired Institute at Syracuse University.

Catania provides an introduction to tentacled snakes and their ingenious ability to capture fish.

Comment on Curr Biol. 2022 Sep 26;32(18):4071-4078.e4.

Neanderthals, our closest extinct relatives, lived in western Eurasia from 400,000 years ago until they went extinct around 40,000 years ago. DNA retrieved from ancient specimens revealed that Neanderthals mated with modern human contemporaries. As a consequence, introgressed Neanderthal DNA survives scattered across the human genome such that 1-4% of the genome of present-day people outside Africa are inherited from Neanderthal ancestors. Patterns of Neanderthal introgressed genomic sequences suggest that Neanderthal alleles had distinct fates in the modern human genetic background. Some Neanderthal alleles facilitated human adaptation to new environments such as novel climate conditions, UV exposure levels and pathogens, while others had deleterious consequences. Here, we review the body of work on Neanderthal introgression over the past decade. We describe how evolutionary forces shaped the genomic landscape of Neanderthal introgression and highlight the impact of introgressed alleles on human biology and phenotypic variation.

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Comment on New Phytol. 2022 Jul 1;:null.

Comment on Nature. 2022 Aug;608(7922):346-352.

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Cognitive models of interval timing can be formulated as an accumulation-to-bound process.1-5 However, the physiological manifestation of such processes has not yet been identified. We used electroencephalography (EEG) to measure the neural responses of participants while they performed a temporal bisection task in which they were requested to categorize the duration of visual stimuli as short or long.6 We found that the stimulus-offset and response-locked activity depends on both stimulus duration and the participants' decision. To relate this activity to the underlying cognitive processes, we used a drift-diffusion model.7 The model includes a noisy accumulator starting with the stimulus onset and a decision threshold. According to the model, a stimulus duration will be categorized as "long" if the accumulator reaches the threshold during stimulus presentation. Otherwise, it will be categorized as "short." We found that at the offset of stimulus presentation, an EEG response marks the distance of the accumulator from the threshold. Therefore, this model offers an accurate description of our behavioral data as well as the EEG response using the same two model parameters. We then replicated this finding in an identical experiment conducted in the tactile domain. We also extended this finding to two different temporal ranges (sub- and supra-second). Taken together, the work provides a new way to study the cognitive processes underlying temporal decisions, using a combination of behavior, EEG, and modeling.

Tool use is a fundamental feature of human evolution. Stone tools are in the archaeological record from 3.4 Ma, even before Homo,1 and the use of stone tools probably predated the split between hominins and panins.2 Using tools (hereafter, tooling cf Fragaszy and Mangalam3) is hypothesized to have improved hominins' foraging efficiency or access to high-quality foods.4-7 This hypothesis is supported if feeding with tools positively contributes to diet quality in extant non-human primates or if foraging efficiency is increased by tooling. However, the contribution of tooling to non-human primates' foraging success has never been investigated through a direct analysis of nutritional ecology.8,9 We used multi-dimensional nutritional geometry to analyze energy and macronutrients (nonstructural carbohydrates, lipids, and protein) in the diets of wild capuchin monkeys (Sapajus libidinous) that routinely crack palm nuts with stone hammers.10,11 We show that eating nuts obtained through tooling helps monkeys to achieve more consistent dietary intakes. Tooling increased the net energy gain by 50% and decreased the proportion of fiber ingested by 7%. Tooling also increased the daily non-protein energy intake. By contrast, protein intake remained constant across foraging days, suggesting a pattern of macronutrient regulation called protein prioritization, which is also found in contemporary humans.8,9 In addition, tooling reduced dispersion in the ratio of protein to non-protein energy, suggesting a role in macronutrient balancing. Our findings suggest that tooling prior to tool making could have substantially increased the nutritional security of ancestral hominins, sowing the seeds for cultural development.5,7 VIDEO ABSTRACT.

For centuries, humans have cultivated cannabis for the pharmacological properties that result from consuming its specialized metabolites, primarily cannabinoids and terpenoids. Today, cannabis is a multi-billion-dollar industry whose existence rests on the biological activity of tiny cell clusters, called glandular trichomes, found mainly on flowers. Cannabinoids are toxic to cannabis cells,1 and how the trichome cells can produce and secrete massive quantities of lipophilic metabolites is not known.1 To address this gap in knowledge, we investigated cannabis glandular trichomes using ultra-rapid cryofixation, quantitative electron microscopy, and immuno-gold labeling of cannabinoid pathway enzymes. We demonstrate that the metabolically active cells in cannabis form a "supercell," with extensive cytoplasmic bridges across the cell walls and a polar distribution of organelles adjacent to the apical surface where metabolites are secreted. The predicted metabolic role of the non-photosynthetic plastids is supported by unusual membrane arrays in the plastids and the localization of the start of the cannabinoid/terpene pathway in the stroma of the plastids. Abundant membrane contact sites connected plastid paracrystalline cores with the plastid envelope, plastid with endoplasmic reticulum (ER), and ER with plasma membrane. The final step of cannabinoid biosynthesis, catalyzed by tetrahydrocannabinolic acid synthase (THCAS), was localized in the cell-surface wall facing the extracellular storage cavity. We propose a new model of how the cannabis cells can support abundant metabolite production, with emphasis on the key role of membrane contact sites and extracellular THCA biosynthesis. This new model can inform synthetic biology approaches for cannabinoid production in yeast or cell cultures.

Comment on Curr Biol. 2022 Sep 26;32(18):3939-3951.e6.

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How the human auditory cortex represents spatially separated simultaneous talkers and how talkers' locations and voices modulate the neural representations of attended and unattended speech are unclear. Here, we measured the neural responses from electrodes implanted in neurosurgical patients as they performed single-talker and multi-talker speech perception tasks. We found that spatial separation between talkers caused a preferential encoding of the contralateral speech in Heschl's gyrus (HG), planum temporale (PT), and superior temporal gyrus (STG). Location and spectrotemporal features were encoded in different aspects of the neural response. Specifically, the talker's location changed the mean response level, whereas the talker's spectrotemporal features altered the variation of response around response's baseline. These components were differentially modulated by the attended talker's voice or location, which improved the population decoding of attended speech features. Attentional modulation due to the talker's voice only appeared in the auditory areas with longer latencies, but attentional modulation due to location was present throughout. Our results show that spatial multi-talker speech perception relies upon a separable pre-attentive neural representation, which could be further tuned by top-down attention to the location and voice of the talker.

Comment in Curr Biol. 2022 Sep 26;32(18):R954-R957.

Comment in Curr Biol. 2022 Sep 26;32(18):R967-R969.

Small poikilotherms such as the fruit fly Drosophila depend on absolute temperature measurements to identify external conditions that are above (hot) or below (cold) their preferred range and to react accordingly. Hot and cold temperatures have a different impact on fly activity and sleep, but the circuits and mechanisms that adjust behavior to specific thermal conditions are not well understood. Here, we use patch-clamp electrophysiology to show that internal thermosensory neurons located within the fly head capsule (the AC neurons1) function as a thermometer active in the hot range. ACs exhibit sustained firing rates that scale with absolute temperature-but only for temperatures above the fly's preferred ∼25°C (i.e., "hot" temperature). We identify ACs in the fly brain connectome and demonstrate that they target a single class of circadian neurons, the LPNs.2 LPNs receive excitatory drive from ACs and respond robustly to hot stimuli, but their responses do not exclusively rely on ACs. Instead, LPNs receive independent drive from thermosensory neurons of the fly antenna via a new class of second-order projection neurons (TPN-IV). Finally, we show that silencing LPNs blocks the restructuring of daytime "siesta" sleep, which normally occurs in response to persistent heat. Our previous work described a distinct thermometer circuit for cold temperature.3 Together, the results demonstrate that the fly nervous system separately encodes and relays absolute hot and cold temperature information, show how patterns of sleep and activity can be adapted to specific temperature conditions, and illustrate how persistent drive from sensory pathways can impact behavior on extended temporal scales.

Comment in Curr Biol. 2022 Sep 26;32(18):R941-R943.

The sleep-wakefulness cycle is regulated by complicated neural networks that include many different populations of neurons throughout the brain. Arginine vasopressin neurons in the paraventricular nucleus of the hypothalamus (PVHAVP) regulate various physiological events and behaviors, such as body-fluid homeostasis, blood pressure, stress response, social interaction, and feeding. Changes in arousal level often accompany these PVHAVP-mediated adaptive responses. However, the contribution of PVHAVP neurons to sleep-wakefulness regulation has remained unknown. Here, we report the involvement of PVHAVP neurons in arousal promotion. Optogenetic stimulation of PVHAVP neurons rapidly induced transitions to wakefulness from both NREM and REM sleep. This arousal effect was dependent on AVP expression in these neurons. Similarly, chemogenetic activation of PVHAVP neurons increased wakefulness and reduced NREM and REM sleep, whereas chemogenetic inhibition of these neurons significantly reduced wakefulness and increased NREM sleep. We observed dense projections of PVHAVP neurons in the lateral hypothalamus with potential connections to orexin/hypocretin (LHOrx) neurons. Optogenetic stimulation of PVHAVP neuronal fibers in the LH immediately induced wakefulness, whereas blocking orexin receptors attenuated the arousal effect of PVHAVP neuronal activation drastically. Monosynaptic rabies-virus tracing revealed that PVHAVP neurons receive inputs from multiple brain regions involved in sleep-wakefulness regulation, as well as those involved in stress response and energy metabolism. Moreover, PVHAVP neurons mediated the arousal induced by novelty stress and a melanocortin receptor agonist melanotan-II. Thus, our data suggested that PVHAVP neurons promote wakefulness via LHOrx neurons in the basal sleep-wakefulness and some stressful conditions.

Comment in Curr Biol. 2022 Sep 26;32(18):R960-R962.

The first asymmetric meiotic cell divisions in mouse oocytes are driven by formin 2 (FMN2)-nucleated actin polymerization around the spindle. In this study, we investigated how FMN2 is recruited to the spindle peripheral ER and how its activity is regulated in mouse meiosis I (MI) oocytes. We show that this process is regulated by the Ran GTPase, a conserved mediator of chromatin signal, and the ER-associated protein VAPA. FMN2 contains a nuclear localization sequence (NLS) within a domain (SLD) previously shown to be required for FMN2 localization to the spindle periphery. FMN2 NLS is bound to the importin α1/β complex, and the disruption of this interaction by RanGTP is required for FMN2 accumulation in the area proximal to the chromatin and the MI spindle. The importin-free FMN2 is then recruited to the surface of ER around the spindle through the binding of the SLD with the ER-membrane protein VAPA. We further show that FMN2 is autoinhibited through an intramolecular interaction between the SLD with the C-terminal formin homology 2 (FH2) domain that nucleates actin filaments. VAPA binding to SLD relieves the autoinhibition of FMN2, leading to localized actin polymerization. This dual control of formin-mediated actin assembly allows actin polymerization to initiate the movement of the meiotic spindle toward the cortex, an essential step in the maturation of the mammalian female gamete.

Comment in Curr Biol. 2022 Sep 26;32(18):R957-R960.

Adenosine triphosphate (ATP) is an abundant and essential metabolite that cells consume and regenerate in large amounts to support growth. Although numerous studies have inferred the intracellular concentration of ATP in bacterial cultures, what happens in individual bacterial cells under stable growth conditions is less clear. Here, we use the QUEEN-2m biosensor to quantify ATP dynamics in single Escherichia coli cells in relation to their growth rate, metabolism, cell cycle, and cell lineage. We find that ATP dynamics are more complex than expected from population studies and are associated with growth-rate variability. Under stable nutrient-rich condition, cells can display large fluctuations in ATP level that are partially coordinated with the cell cycle. Abrogation of aerobic acetate fermentation (overflow metabolism) through genetic deletion considerably reduces both the amplitude of ATP level fluctuations and the cell-cycle trend. Similarly, growth in media in which acetate fermentation is lower or absent results in the reduction of ATP level fluctuation and cell-cycle trend. This suggests that overflow metabolism exhibits temporal dynamics, which contributes to fluctuating ATP levels during growth. Remarkably, at the single-cell level, growth rate negatively correlates with the amplitude of ATP fluctuation for each tested condition, linking ATP dynamics to growth-rate heterogeneity in clonal populations. Our work highlights the importance of single-cell analysis in studying metabolism and its implication to phenotypic diversity and cell growth.

Plant diseases cause a huge impact on food security and are of global concern. While application of agrochemicals is a common approach in the control of plant diseases currently, growing drug resistance and the impact of off-target effects of these compounds pose major challenges. The identification of pathogenicity-related virulence mechanisms and development of new chemicals that target these processes are urgently needed. One such virulence mechanism is the detoxification of reactive oxygen species (ROS) generated by host plants upon attack by pathogens. The machinery of ROS detoxification might therefore serve as a drug target for preventing plant diseases, but few anti-ROS-scavenging drugs have been developed. Here, we show that in the model system Botrytis cinerea secretion of the cytochrome c-peroxidase, BcCcp1 removes plant-produced H2O2 and promotes pathogen invasion. The peroxidase secretion is modulated by a Tom1-like protein, BcTol1, through physical interaction. We show that BcTol1 is regulated at different levels to enhance the secretion of BcCcp1 during the early infection stage. Inactivation of either BcTol1 or BcCcp1 leads to dramatically reduced virulence of B. cinerea. We identify two BcTol1-targeting small molecules that not only prevent B. cinerea invasion but also have effective activity against a wide range of plant fungal pathogens without detectable effect on the hosts. These findings reveal a conserved mechanism of ROS detoxification in fungi and provide a class of potential fungicides to control diverse plant diseases. The approach described here has wide implications for further drug discovery in related fields.

The maturation of sleep behavior across a lifespan (sleep ontogeny) is an evolutionarily conserved phenomenon. Mammalian studies have shown that in addition to increased sleep duration, early life sleep exhibits stark differences compared with mature sleep with regard to sleep states. How the intrinsic maturation of sleep output circuits contributes to sleep ontogeny is poorly understood. The fruit fly Drosophila melanogaster exhibits multifaceted changes to sleep from juvenile to mature adulthood. Here, we use a non-invasive probabilistic approach to investigate the changes in sleep architecture in juvenile and mature flies. Increased sleep in juvenile flies is driven primarily by a decreased probability of transitioning to wake and characterized by more time in deeper sleep states. Functional manipulations of sleep-promoting neurons in the dorsal fan-shaped body (dFB) suggest that these neurons differentially regulate sleep in juvenile and mature flies. Transcriptomic analysis of dFB neurons at different ages and a subsequent RNAi screen implicate the genes involved in dFB sleep circuit maturation. These results reveal that the dynamic transcriptional states of sleep output neurons contribute to the changes in sleep across the lifespan.

Associative brain centers, such as the insect mushroom body, need to represent sensory information in an efficient manner. In Drosophila melanogaster, the Kenyon cells of the mushroom body integrate inputs from a random set of olfactory projection neurons, but some projection neurons-namely those activated by a few ethologically meaningful odors-connect to Kenyon cells more frequently than others. This biased and random connectivity pattern is conceivably advantageous, as it enables the mushroom body to represent a large number of odors as unique activity patterns while prioritizing the representation of a few specific odors. How this connectivity pattern is established remains largely unknown. Here, we test whether the mechanisms patterning the connections between Kenyon cells and projection neurons depend on sensory activity or whether they are hardwired. We mapped a large number of mushroom body input connections in partially anosmic flies-flies lacking the obligate odorant co-receptor Orco-and in wild-type flies. Statistical analyses of these datasets reveal that the random and biased connectivity pattern observed between Kenyon cells and projection neurons forms normally in the absence of most olfactory sensory activity. This finding supports the idea that even comparatively subtle, population-level patterns of neuronal connectivity can be encoded by fixed genetic programs and are likely to be the result of evolved prioritization of ecologically and ethologically salient stimuli.

Comment on Curr Biol. 2022 Sep 26;32(18):3898-3910.e14.

Chao Fang and Fanjiang Kong introduce the polyploid staple crop, soybean - a major source of dietary protein and oil and model species for root nodulation and plant-developmental studies.

Interview with David Kleinfeld, who leads the Neurophysics laboratory at UC San Diego.

Transposable elements are known by many names, including 'transposons', 'interspersed repeats', 'selfish genetic elements', 'jumping genes', and 'parasitic DNA', but here we will refer to them simply as transposable elements. Many biologists will have heard of transposable elements and their ability to transpose (change position) within the genome. But fewer may be aware of their varied influences on host biology, including contributions to the evolution of diverse host traits such as internal gestation, memory, colouration, and adaptive immunity. Transposable elements are a near ubiquitous feature of eukaryotic genomes, and they often comprise a substantial proportion of total genomic content. Consequently, transposable element genes are considered among the most abundant coding sequences in nature. Recent advances in genome sequencing have ushered in a golden age for transposable-element research, providing opportunities to greatly improve our understanding of the effects of transposable elements on host evolution and disease. However, our ability to detect and analyse transposable elements still faces significant challenges, impairing efforts to decipher their evolution, characterise their diversity, and elucidate their myriad host influences. Below, we summarise key aspects of transposable element biology in eukaryotes and discuss major outstanding research questions.

Comment on Nature. 2022 Jun;606(7913):329-334.

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Comment in Lab Anim (NY). 2022 Nov;51(11):289-290.

Cells are complex biochemical systems whose behaviors emerge from interactions among myriad molecular components. Computation is often invoked as a general framework for navigating this cellular complexity. However, it is unclear how cells might embody computational processes such that the theories of computation, including finite-state machine models, could be productively applied. Here, we demonstrate finite-state-machine-like processing embodied in cells using the walking behavior of Euplotes eurystomus, a ciliate that walks across surfaces using fourteen motile appendages (cirri). We found that cellular walking entails regulated transitions among a discrete set of gait states. The set of observed transitions decomposes into a small group of high-probability, temporally irreversible transitions and a large group of low-probability, time-symmetric transitions, thus revealing stereotypy in the sequential patterns of state transitions. Simulations and experiments suggest that the sequential logic of the gait is functionally important. Taken together, these findings implicate a finite-state-machine-like process. Cirri are connected by microtubule bundles (fibers), and we found that the dynamics of cirri involved in different state transitions are associated with the structure of the fiber system. Perturbative experiments revealed that the fibers mediate gait coordination, suggesting a mechanical basis of gait control.

Comment on Curr Biol. 2022 Sep 12;32(17):3862-3870.e6.

Density-dependent prey depletion around breeding colonies has long been considered an important factor controlling the population dynamics of colonial animals.1-4 Ashmole proposed that as seabird colony size increases, intraspecific competition leads to declines in reproductive success, as breeding adults must spend more time and energy to find prey farther from the colony.1 Seabird colony size often varies over several orders of magnitude within the same species and can include millions of individuals per colony.5,6 As such, colony size likely plays an important role in determining the individual behavior of its members and how the colony interacts with the surrounding environment.6 Using tracking data from murres (Uria spp.), the world's most densely breeding seabirds, we show that the distribution of foraging-trip distances scales to colony size0.33 during the chick-rearing stage, consistent with Ashmole's halo theory.1,2 This pattern occurred across colonies varying in size over three orders of magnitude and distributed throughout the North Atlantic region. The strong relationship between colony size and foraging range means that the foraging areas of some colonial species can be estimated from colony sizes, which is more practical to measure over a large geographic scale. Two-thirds of the North Atlantic murre population breed at the 16 largest colonies; by extrapolating the predicted foraging ranges to sites without tracking data, we show that only two of these large colonies have significant coverage as marine protected areas. Our results are an important example of how theoretical models, in this case, Ashmole's version of central-place-foraging theory, can be applied to inform conservation and management in colonial breeding species.

Foraging innovations can give wild animals access to human-derived food sources1. If these innovations spread, they can enable adaptive flexibility2 but also lead to human-wildlife conflicts3. Examples include crop-raiding elephants4 and long-tailed macaques that steal items from people to trade them back for food5. Behavioural responses by humans might act as a further driver on animal innovation2,6, even potentially leading to an inter-species 'innovation arms-race'7, yet this is almost entirely unexplored. Here, we report a potential case in wild, urban-living, sulphur-crested cockatoos (Cacatua galerita; henceforth cockatoos), where the socially-learnt behaviour of opening and raiding of household bins by cockatoos8 is met with increasingly effective and socially-learnt bin-protection measures by human residents.

Sweet and bitter compounds excite different sensory cells and drive opposing behaviors. However, it remains unclear how sweet and bitter tastes are represented by the neural circuits linking sensation to behavior. To investigate this question in Drosophila, we devised trans-Tango(activity), a strategy for calcium imaging of second-order gustatory projection neurons based on trans-Tango, a genetic transsynaptic tracing technique. We found spatial overlap between the projection neuron populations activated by sweet and bitter tastants. The spatial representation of bitter tastants in the projection neurons was consistent, while that of sweet tastants was heterogeneous. Furthermore, we discovered that bitter tastants evoke responses in the gustatory receptor neurons and projection neurons upon both stimulus onset and offset and that bitter offset and sweet onset excite overlapping second-order projections. These findings demonstrate an unexpected complexity in the representation of sweet and bitter tastants by second-order neurons of the gustatory circuit.

Sensory systems display remarkable plasticity and are under strong evolutionary selection. The Mexican cavefish, Astyanax mexicanus, consists of eyed river-dwelling surface populations and multiple independent cave populations that have converged on eye loss, providing the opportunity to examine the evolution of sensory circuits in response to environmental perturbation. Functional analysis across multiple transgenic populations expressing GCaMP6s showed that functional connectivity of the optic tectum largely did not differ between populations, except for the selective loss of negatively correlated activity within the cavefish tectum, suggesting positively correlated neural activity is resistant to an evolved loss of input from the retina. Furthermore, analysis of surface-cave hybrid fish reveals that changes in the tectum are genetically distinct from those encoding eye loss. Together, these findings uncover the independent evolution of multiple components of the visual system and establish the use of functional imaging in A. mexicanus to study neural circuit evolution.

Cryptochrome (CRY) is a short-wavelength light-sensitive photoreceptor expressed in a subset of circadian neurons and eyes in Drosophila that regulates light-evoked circadian clock resetting. Acutely, light evokes rapid electrical excitation of the ventral lateral subset of circadian neurons and confers circadian-modulated avoidance behavioral responses to short-wavelength light. Recent work shows dramatically different avoidance versus attraction behavioral responses to short-wavelength light in day-active versus night-active mosquitoes and that these behavioral responses are attenuated by CRY protein degradation by constant light exposure in mosquitoes. To determine whether CRY1s mediate species-specific coding for behavioral and electrophysiological light responses, we used an "empty neuron" approach and transgenically expressed diurnal Aedes aegypti (AeCRY1) versus nocturnal Anopheles gambiae (AgCRY1) in a cry-null Drosophila background. AeCRY1 is much less light sensitive than either AgCRY1 or DmCRY as shown by partial behavioral rhythmicity following constant light exposure. Remarkably, expression of nocturnal AgCRY1 confers low survival to constant white light as does expression of AeCRY1 to a lesser extent. AgCRY1 mediates significantly stronger electrophysiological cell-autonomous responses to 365 nm ultraviolet (UV) light relative to AeCRY1. AgCRY1 expression mediates electrophysiological sensitivity to 635 nm red light, whereas AeCRY1 does not, consistent with species-specific mosquito red light responses. AgCRY1 and DmCRY mediate intensity-dependent avoidance behavior to UV light at different light intensity thresholds, whereas AeCRY1 does not, thus mimicking mosquito and fly behaviors. These findings highlight CRY as a key non-image-forming visual photoreceptor that mediates physiological and behavioral light responses in a species-specific fashion.

Insect pollination is one of the hallmarks of flowering plants.1 Bees, moths, flies, and some other pollinators evolved elongate siphonate mouthparts for sucking concealed nectar and occasionally other liquids.2 However, it is clear from the fossil record that insects with similar adaptations appeared long before the mid-Cretaceous radiation of angiosperms. These insects most probably used their proboscis to reach pollination drops and other sugary fluids that were hidden in the cones of extinct gymnosperms, pollinating them in the process.3-6 The vast majority of these gymnosperm-associated long-proboscid insects have been reported from the Middle Jurassic to the Early Cretaceous, i.e., the time interval that immediately predated the advent of flowering plants.7 By contrast, the Paleozoic stage of the co-evolution between long-proboscid insect pollinators and plants has remained poorly understood. Here, we report a putative pollination mutualism involving long-proboscid holometabolous insects (Panorpida: Protomeropidae) from the Early Permian of Russia (ca. 283-273 Ma). Their elongate mouthparts have very similar morphology to those of some present-day nectarivorous Coleoptera and Hymenoptera and probably served to imbibe micropylar secretions from the semi-closed ovulate organs of the gymnosperms of a peltaspermalean affinity that have been found in the same locality. This is the earliest record of insects with siphonate-like mouthparts, which could indicate that the complex interactions between pollinators and gymnosperms predate the first flowering plants by over 100 Ma.

Although scales are a defining and conspicuous feature of moths and butterflies (Lepidoptera),1-3 their earliest evolution predates the group but is shrouded by a dearth of fossil evidence. Herein, we report two new species in mid-Cretaceous Kachin amber, representing lineages closely related to Lepidoptera: one represents the extinct Tarachoptera, with dense scales on the fore- and hindwings, while the other is an early lineage of caddisflies, with a hindwing covered by a single layer of angustifoliate scales. A novel phylogenetic analysis of 174 morphological characters and 73 extant and fossil representatives of Mecopterida demonstrates a monophyletic origin of scales in the common ancestor of Tarachoptera, Trichoptera, and Lepidoptera; that Tarachoptera are monophyletic but their scale morphology is plesiomorphic for the whole group; and that scales were lost early in caddisfly evolution before reappearing multiple times within the clade. Collectively, these fossils provide clarity into the origin and early evolution of scales before their diversification among the moths and butterflies.

Comment in Curr Biol. 2022 Sep 12;32(17):R931-R934.

Comment in Curr Biol. 2022 Sep 12;32(17):R921-R923.

Comment in Curr Biol. 2022 Sep 12;32(17):R926-R928.

Sponges, among the oldest extant multicellular organisms on Earth,1 play a key role in the cycling of nutrients in many aquatic ecosystems.2-5 They need to employ strategies to prevent clogging of their internal filter system by solid wastes,6-8 but self-cleaning mechanisms are largely unknown. It is commonly assumed that sponges remove solid waste with the outflowing water through distinct outflow openings (oscula).3,9 Here, we present time-lapse video footage and analyses of sponge waste revealing a completely different mechanism of particle removal in the Caribbean tube sponge Aplysina archeri. This sponge actively moves particle-trapping mucus against the direction of its internal water flow and ejects it into the surrounding water from its seawater inlet pores (ostia) through periodic surface contractions that have been described earlier as "sneezing."10,11 Visually, it appears as if the sponge is continuously streaming mucus-embedded particles and sneezes to shed this particulate waste, resulting in a notable flux of detritus that is actively consumed by sponge-associated fauna. The new data are used to estimate production of detritus for this abundant sponge on Caribbean coral reefs. Last, we discuss why waste removal from the sponge inhalant pores may be a common feature among sponges and compare the process in sponges to equivalent mechanisms of mucus transport in other animals, including humans.

Common cortico-basal ganglia models of motor control suggest a key role for the subthalamic nucleus (STN) in motor inhibition.1-3 In particular, when already-initiated actions have to be suddenly stopped, the STN is purportedly recruited via a hyperdirect pathway to net inhibit the cortico-motor system in a broad, non-selective fashion.4 Indeed, the suppression of cortico-spinal excitability (CSE) during rapid action stopping extends beyond the stopped muscle and affects even task-irrelevant motor representations.5,6 Although such non-selective CSE suppression has long been attributed to the broad inhibitory influence of STN on the motor system, causal evidence for this association is hitherto lacking. Here, 20 Parkinson's disease patients treated with STN deep-brain stimulation (DBS) and 20 matched healthy controls performed a verbal stop-signal task while CSE was measured from a task-unrelated hand muscle. DBS allowed a causal manipulation of STN, while CSE was measured using transcranial magnetic stimulation (TMS) over primary motor cortex and concurrent electromyography. In patients OFF-DBS and controls, the CSE of the hand was non-selectively suppressed when the verbal response was successfully stopped. Crucially, this effect disappeared when STN was disrupted via DBS in the patient group. Using this unique combination of DBS and TMS during human behavior, the current study provides first causal evidence that STN is likely involved in non-selectively suppressing the physiological excitability of the cortico-motor system during action stopping. This confirms a core prediction of long-held cortico-basal ganglia circuit models of movement. The absence of cortico-motor inhibition during STN-DBS may also provide potential insights into the common side effects of STN-DBS, such as increased impulsivity.7-11.

A key aim in biology is to identify which genetic changes contributed to the evolution of form through time. Apical dominance, the inhibitory effect exerted by shoot apices on the initiation or outgrowth of distant lateral buds, is a major regulatory mechanism of plant form.1 Nearly a century of studies in the sporophyte of flowering plants have established the phytohormone auxin as a front-runner in the search for key factors controlling apical dominance,2,3 identifying critical roles for long-range polar auxin transport and local auxin biosynthesis in modulating shoot branching.4-10 A capacity for lateral branching evolved by convergence in the gametophytic shoot of mosses and primed its diversification;11 however, polar auxin transport is relatively unimportant in this developmental process,12 the contribution of auxin biosynthesis genes has not been assessed, and more generally, the extent of conservation in apical dominance regulation within the land plants remains largely unknown. To fill this knowledge gap, we sought to identify genetic determinants of apical dominance in the moss Physcomitrium patens. Here, we show that leafy shoot apex decapitation releases apical dominance through massive and rapid transcriptional reprogramming of auxin-responsive genes and altering auxin biosynthesis gene activity. We pinpoint a subset of P. patens TRYPTOPHAN AMINO-TRANSFERASE (TAR) and YUCCA FLAVIN MONOOXYGENASE-LIKE (YUC) auxin biosynthesis genes expressed in the main and lateral shoot apices and show that they are essential for coordinating branch initiation and outgrowth. Our results demonstrate that local auxin biosynthesis acts as a pivotal regulator of apical dominance in moss and constitutes a shared mechanism underpinning shoot architecture control in land plants.

Comment in Curr Biol. 2022 Sep 12;32(17):R912-R914.

A major challenge for neuroscience, public health, and evolutionary biology is to understand the effects of scarcity and uncertainty on the developing brain. Currently, a significant fraction of children and adolescents worldwide experience insecure access to food. The goal of our work was to test in mice whether the transient experience of insecure versus secure access to food during the juvenile-adolescent period produced lasting differences in learning, decision-making, and the dopamine system in adulthood. We manipulated feeding schedules in mice from postnatal day (P)21 to P40 as food insecure or ad libitum and found that when tested in adulthood (after P60), males with different developmental feeding history showed significant differences in multiple metrics of cognitive flexibility in learning and decision-making. Adult females with different developmental feeding history showed no differences in cognitive flexibility but did show significant differences in adult weight. We next applied reinforcement learning models to these behavioral data. The best fit models suggested that in males, developmental feeding history altered how mice updated their behavior after negative outcomes. This effect was sensitive to task context and reward contingencies. Consistent with these results, in males, we found that the two feeding history groups showed significant differences in the AMPAR/NMDAR ratio of excitatory synapses on nucleus-accumbens-projecting midbrain dopamine neurons and evoked dopamine release in dorsal striatal targets. Together, these data show in a rodent model that transient differences in feeding history in the juvenile-adolescent period can have significant impacts on adult weight, learning, decision-making, and dopamine neurobiology.

Producing context-appropriate motor acts requires integrating multiple sensory modalities. Presynaptic inhibition of proprioceptive afferent neurons1-4 and afferents of different modalities targeting the same motor neurons (MNs)5-7 underlies some of this integration. However, in most systems, an interneuronal network is interposed between sensory afferents and MNs. How these networks contribute to this integration, particularly at single-neuron resolution, is little understood. Context-specific integration of load and movement sensory inputs occurs in the stick insect locomotory system,6,8-12 and both inputs feed into a network of premotor nonspiking interneurons (NSIs).8 We analyzed how load altered movement signal processing in the stick insect femur-tibia (FTi) joint control system by tracing the interaction of FTi movement13-15 (femoral chordotonal organ [fCO]) and load13,15,16 (tibial campaniform sensilla [CS]) signals through the NSI network to the slow extensor tibiae (SETi) MN, the extensor MN primarily active in non-walking animals.17-19 On the afferent level, load reduced movement signal gain by presynaptic inhibition. In the NSI network, graded responses to movement and load inputs summed nonlinearly, increasing the gain of NSIs opposing movement-induced reflexes and thus decreasing the SETi and extensor tibiae muscle movement reflex responses. Gain modulation was movement-parameter specific and required presynaptic inhibition. These data suggest that gain changes in distributed premotor networks, specifically the relative weighting of antagonistic pathways, could be a general mechanism by which multiple sensory modalities are integrated to generate context-appropriate motor activity.

Comment on Cell. 2022 Aug 18;185(17):3248-3262.e20.

Comment in Curr Biol. 2022 Sep 12;32(17):R914-R916.

Neurons integrate excitatory and inhibitory signals to produce their outputs, but the role of input timing in this integration remains poorly understood. Motion detection is a paradigmatic example of this integration, since theories of motion detection rely on different delays in visual signals. These delays allow circuits to compare scenes at different times to calculate the direction and speed of motion. Different motion detection circuits have different velocity sensitivity, but it remains untested how the response dynamics of individual cell types drive this tuning. Here, we sped up or slowed down specific neuron types in Drosophila's motion detection circuit by manipulating ion channel expression. Altering the dynamics of individual neuron types upstream of motion detectors increased their sensitivity to fast or slow visual motion, exposing distinct roles for excitatory and inhibitory dynamics in tuning directional signals, including a role for the amacrine cell CT1. A circuit model constrained by functional data and anatomy qualitatively reproduced the observed tuning changes. Overall, these results reveal how excitatory and inhibitory dynamics together tune a canonical circuit computation.

Comment in Curr Biol. 2022 Sep 12;32(17):R916-R918.