Current Biology最新文献

Visual simulation-i.e., using internal reconstructions of the world to experience potential future versions of events that are not currently happening-is among the most sophisticated capacities of the human mind. But is this ability in fact uniquely human? To answer this question, we tested monkeys on a series of experiments involving the "Planko" game, which we have previously used to evoke visual simulation in human participants. We found that monkeys were able to successfully play the game using a simulation strategy, predicting the trajectory of a ball through a field of planks while demonstrating a level of accuracy and behavioral signatures comparable with those of humans. Computational analyses further revealed that the monkeys' strategy while playing Planko aligned with a recurrent neural network (RNN) that approached the task using a spontaneously learned simulation strategy. Finally, we carried out awake functional magnetic resonance imaging while monkeys played Planko. We found activity in motion-sensitive regions of the monkey brain during hypothesized simulation periods, even without any perceived visual motion cues. This neural result closely mirrors previous findings from human research, suggesting a shared mechanism of visual simulation across species. Taken together, these findings challenge traditional views of animal cognition, proposing that nonhuman primates possess a complex cognitive landscape, capable of invoking imaginative and predictive mental experiences to solve complex everyday problems.

In nature, organisms experience combinations of stressors. However, laboratory studies use batch cultures, which simplify reality and focus on population-level responses to individual stressors.^1,2,3,4,5 In recent years, bacterial stress responses have been examined with single-cell resolution using microfluidics.^{6,7,8,9,10,11,12} Here, we use a microfluidic approach to simultaneously provide a physical stressor (shear flow) and a chemical stressor (H₂O₂) to the human pathogen Pseudomonas aeruginosa. By treating cells with levels of flow and H₂O₂ that commonly co-occur in human host tissues,^{13,14,15,16,17,18} we discover that previous reports significantly overestimate the H₂O₂ levels required to block bacterial growth. Specifically, we establish that flow increases H₂O₂ effectiveness 50-fold, explaining why previous studies lacking flow required much higher concentrations. Using natural H₂O₂ levels, we identify the core H₂O₂ regulon, characterize OxyR-mediated dynamic regulation, and demonstrate that multiple H₂O₂ scavenging systems have redundant roles. By examining single-cell behavior, we serendipitously discover that the combined effects of H₂O₂ and flow block pilus-driven surface migration. Thus, our results counter previous studies and reveal that natural levels of H₂O₂ and flow synergize to restrict bacterial motility and survival. By studying two stressors at once, our research highlights the limitations of oversimplifying nature and demonstrates that physical and chemical stress can combine to yield unpredictable effects.

Echolocating bats rely on rapid processing of auditory information to guide moment-to-moment decisions related to echolocation call design and flight path selection. The fidelity of sonar echoes, however, can be disrupted in natural settings due to occlusions, noise, and conspecific jamming signals. Behavioral sensorimotor adaptation to external blocks of relevant cues has been studied extensively, but little is known about adaptations that mitigate internal sensory flow interruption. How do bats modify their sensory-guided behaviors in natural tasks when central auditory processing is interrupted? Here, we induced internal sensory interruptions by reversibly inactivating excitatory neurons in the inferior colliculus (IC) using ligand-activated inhibitory designer receptors exclusively activated by designer drugs (DREADDs). Bats were trained to navigate through one of three open windows in a curtain to obtain a food reward, while their echolocation and flight behaviors were quantified with synchronized ultrasound microphone and stereo video recordings. Under control conditions, bats reliably steered through the open window, only occasionally contacting the curtain edge. Suppressing IC excitatory activity elevated hearing thresholds, disrupted overall performance in the task, increased the frequency of curtain contact, and led to striking compensatory sensorimotor adjustments. DREADDs-treated bats modified flight trajectories to maximize returning echo information and adjusted sonar call design to boost detection of obstacles. Sensorimotor adaptations appeared immediately and did not change over successive trials, suggesting that these behavioral adaptations are mediated through existing neural circuitry. Our findings highlight the remarkable rapid adaptive strategies bats employ to compensate for internal sensory interruptions to effectively navigate their environments.

Endosymbiosis-where a microbe lives and replicates within a host-is an important contributor to organismal function that has accelerated evolutionary innovations and catalyzed the evolution of complex life. The evolutionary processes associated with transitions to endosymbiosis, however, are poorly understood. Here, we leverage the wide diversity of host-associated lifestyles of the genus Arsenophonus to reveal the complex evolutionary processes that occur during the transition to a vertically transmitted endosymbiotic lifestyle from strains maintained solely by horizontal (infectious) transmission. We compared the genomes of 38 strains spanning diverse lifestyles from horizontally transmitted pathogens to obligate interdependent endosymbionts. Among culturable strains, we observed those with vertical transmission had larger genome sizes than closely related horizontally transmitting counterparts, consistent with evolutionary innovation and the rapid gain of new functions. Increased genome size was a consequence of prophage and plasmid acquisition, including a cargo of type III effectors, alongside the concomitant loss of CRISPR-Cas genome defense systems, enabling mobile genetic element expansion. Persistent endosymbiosis was also associated with loss of type VI secretion, which we hypothesize to be a consequence of reduced microbe-microbe competition. Thereafter, the transition to endosymbiosis with strict vertical inheritance was associated with the expected relaxation of purifying selection, gene pseudogenization, metabolic degradation, and genome reduction. We argue that reduced phage predation in endosymbiotic niches drives the loss of genome defense systems driving rapid genome expansion upon the adoption of endosymbiosis and vertical transmission. This remodeling enables rapid horizontal gene transfer-mediated evolutionary innovation and precedes the reductive evolution traditionally associated with adaptation to endosymbiosis.

Maintenance of lysosomal integrity is essential for cell viability. Upon injury, lysosomes may be targeted for degradation via a selective form of autophagy known as lysophagy. The engulfment of a damaged lysosome by an autophagosome is mediated by the recruitment of adaptor proteins, including SQSTM1/p62. p62 promotes lysophagy via the formation of phase-separated condensates in a mechanism that is regulated by the heat shock protein HSP27. Here, we demonstrate a direct interaction between HSP27 and p62. We used structural modeling to predict the binding interface between HSP27 and p62 and identify several disease-associated mutations that map to this interface. We used proteomics to identify post-translational modifications of HSP27 that regulate HSP27 recruitment to stressed lysosomes, finding robust phosphorylation at several serine residues. Next, we characterized the upstream signaling mechanism leading to HSP27 phosphorylation and found that p38 mitogen-activated protein kinase (MAPK) and its effector kinase MAP kinase-activated protein kinase 2 (MK2) are activated upon lysosomal damage by the kinase mTOR and the production of intracellular reactive oxygen species (ROS). Increased ROS activates p38 MAPK, which in turn allows MK2-dependent phosphorylation of HSP27. Depletion of HSP27 or the inhibition of HSP27 phosphorylation alters the dynamics of p62 condensates on stressed lysosomes, significantly inhibiting p62-dependent lysophagy. Thus, we define a novel lysosomal quality control mechanism in which lysosomal injury triggers a p38 MAPK/MK2 signaling cascade promoting p62-dependent lysophagy. Further, this signaling cascade is activated by many cellular stressors, including oxidative and heat stress, suggesting that other forms of selective autophagy may be regulated by p38 MAPK/MK2/HSP27.

In the open ocean, achieving camouflage is complicated by the fact that the downwelling light is generally much brighter than the upwelling light, which means that any object, even if its ventral surface is white due to countershading, will appear as a dark silhouette when viewed from below.^1,2,3 To overcome this, many marine species employ counterillumination, whereby light is emitted from photophores on their ventral surface to replace the downwelling light blocked by their body.^4,5,6 However, only a single behavioral study has tested the efficacy of counterillumination as an anti-predation strategy.⁷ Counterillumination is predicted to be particularly useful against predators that have poor visual acuity and lack color vision,⁸ like the Great White shark (Carcharodon carcharias), the species responsible for most human shark-bite fatalities globally.⁹ Here, we take inspiration from nature to show that counterillumination can prevent Great White sharks from attacking artificial seal decoys. Using seal decoys fitted with LED lights and towed behind a boat, we explored the efficiency of different light configurations on the deterrence effect, showing that visual shape and motion cues are critical for prey recognition by Great White sharks. Counterillumination that is brighter than the background is most effective in deterring sharks, implying that, in this context, counterillumination works through disruptive camouflage rather than background matching. Our results reveal the importance of a dark silhouette against a lighter background in predatory behavior in Great White sharks and that altering the silhouette may form the basis of new non-invasive shark deterrent technology to protect human life. VIDEO ABSTRACT.

Cortical populations often exhibit changes in activity even when behavior is stable. How behavioral stability is maintained in the face of such "representational drift" remains unclear. One possibility is that some neurons are more stable than others. We examined whisker touch responses in layers 2-4 of the primary vibrissal somatosensory cortex (vS1) over several weeks in mice stably performing an object detection task with two whiskers. Although the number of touch neurons remained constant, individual neurons changed with time. Touch-responsive neurons with broad receptive fields were more stable than narrowly tuned neurons. Transitions between functional types were non-random: before becoming broadly tuned, unresponsive neurons first passed through a period of narrower tuning. Broadly tuned neurons in layers 2 and 3 with higher pairwise correlations to other touch neurons were more stable than neurons with lower correlations. Thus, a small population of broadly tuned and synchronously active touch neurons exhibits elevated stability and may be particularly important for behavior.

Punishing and rewarding experiences can change the valence of sensory stimuli and guide animal behavior in opposite directions, resulting in avoidance or approach. Often, however, a stimulus is encountered with both positive and negative experiences. How is such conflicting information represented in the brain and resolved into a behavioral decision? We address this question by dissecting a circuit for sexual conditioning in C. elegans. In this learning paradigm, an odor is conditioned with both a punishment (starvation) and a reward (mates), resulting in odor approach. We find that negative and positive experiences are both encoded by the neuropeptide pigment dispersing factor 1 (PDF-1) being released from, and acting on, different neurons. Each experience creates a distinct memory in the circuit for odor processing. This results in the sensorimotor representation of the odor being different in naive and sexually conditioned animals, despite both displaying approach. Our results reveal that the positive valence of a stimulus is not represented in the activity of any single neuron class but flexibly represented within the circuit according to the experiences and predictions associated with the stimulus.

Since Jane Goodall's famous observations of stick tool use by chimpanzees,¹ animal tool use has been observed in numerous species, including many primates, dolphins, and birds. Some animals, such as New Caledonian crows, even craft tools.^2,3 Elephants frequently use tools^4,5 and also modify them.⁶ We studied water-hose tool use in Asian zoo elephants. Flexibility, extension, and water flow make hoses exceptionally complex tools. Individual elephants differed markedly in their water-hose handling. Female elephant Mary displayed sophisticated hose-showering behaviors. She showed lateralized hose handling, systematically showered her body, and coordinated the trunk-held water hose with limb behaviors. Mary usually grasped the hose behind the tip, using it as a stiff shower head. To reach her back, however, she grasped the hose further from the tip and swung it on her back, using hose flexibility and ballistics. Aggressive interactions between Mary and the younger female elephant, Anchali, ensued around Mary's showering time. At some point, Anchali started pulling the water hose toward herself, lifting and kinking it, then regrasping and compressing the kink. This kink-and-clamp behavior disrupted water flow and was repeated in several sessions as a strict sequence of maneuvers. The efficacy of water flow disruption increased over time. In control experiments with multiple hoses, it was not clear whether Anchali specifically targeted Mary's showering hose. We also observed Anchali pressing down on the water hose, performing an on-hose trunk stand, which also disrupted water flow. We conclude that elephants show sophisticated hose tool use and manipulation. VIDEO ABSTRACT.