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Acyl coenzyme A binding protein (ACBP), also known as diazepam binding inhibitor (DBI) is a multifunctional protein with an intracellular action (as ACBP), as well as with an extracellular role (as DBI). The plasma levels of soluble ACBP/DBI are elevated in human obesity and reduced in anorexia nervosa. Accumulating evidence indicates that genetic or antibody-mediated neutralization of ACBP/DBI has anorexigenic effects, thus inhibiting food intake and inducing lipo-catabolic reactions in mice. A number of anorexiants have been withdrawn from clinical development because of their side effects including an increase in depression and suicide. For this reason, we investigated the psychiatric impact of ACBP/DBI in mouse models and patient cohorts. Intravenously (i.v.) injected ACBP/DBI protein conserved its orexigenic function when the protein was mutated to abolish acyl coenzyme A binding, but lost its appetite-stimulatory effect in mice bearing a mutation in the γ2 subunit of the γ-aminobutyric acid (GABA) A receptor (GABA A R). ACBP/DBI neutralization by intraperitoneal (i.p.) injection of a specific mAb blunted excessive food intake in starved and leptin-deficient mice, but not in ghrelin-treated animals. Neither i.v. nor i.p. injected anti-ACBP/DBI antibody affected the behavior of mice in the dark–light box and open-field test. In contrast, ACBP/DBI increased immobility in the forced swim test, while anti-ACBP/DBI antibody counteracted this sign of depression. In patients diagnosed with therapy-resistant bipolar disorder or schizophrenia, ACBP/DBI similarly correlated with body mass index (BMI), not with the psychiatric diagnosis. Patients with high levels of ACBP/DBI were at risk of dyslipidemia and this effect was independent from BMI, as indicated by multivariate analysis. In summary, it appears that ACBP/DBI neutralization has no negative impact on mood and that human depression is not associated with alterations in ACBP/DBI concentrations.

The harmful effects of perfluorooctane sulfonate (PFOS) are of growing international concern. This paper aimed to gain an integrated understanding of fitness-related ecological end points, such as behavior, metabolism and swimming physiology, in juvenile Spinibarbus sinensis in response to PFOS toxicity at different temperatures. The fish were exposed to a range of PFOS concentrations (0, 0.32, 0.8, 2 and 5 mg/L) at different temperatures (18 and 28 °C) for 30 days. The effects on fish behavior, metabolic characteristics and aerobic swimming performance caused by PFOS at different temperatures were investigated. Our results showed that both PFOS and temperature had important influences on spontaneous swimming behavior, social interactions, routine metabolic rate (RMR), net energetic cost of transport (COT net ) and critical swimming speed ( U crit ) in fish. The lowest observed effect concentration for both U crit and RMR was 5 and 0.8 mg/L at 18 and 28 °C, respectively. We found that PFOS affected various behavioral and social end points and also appeared to affect metabolic rates and reduced U crit , likely as a result of increased COT net , and that many of these effects also changed with respect to temperature. Our results further the understanding of the metabolic and behavioral toxicity of PFOS to aquatic organisms.

Fishes exhibit an astounding diversity of locomotor behaviors from classic swimming with their body and fins to jumping, flying, walking, and burrowing. Fishes that use their body and caudal fin (BCF) during undulatory swimming have been traditionally divided into modes based on the length of the propulsive body wave and the ratio of head:tail oscillation amplitude: anguilliform, subcarangiform, carangiform, and thunniform. This classification was first proposed based on key morphological traits, such as body stiffness and elongation, to group fishes based on their expected swimming mechanics. Here, we present a comparative study of 44 diverse species quantifying the kinematics and morphology of BCF-swimming fishes. Our results reveal that most species we studied share similar oscillation amplitude during steady locomotion that can be modeled using a second-degree order polynomial. The length of the propulsive body wave was shorter for species classified as anguilliform and longer for those classified as thunniform, although substantial variability existed both within and among species. Moreover, there was no decrease in head:tail amplitude from the anguilliform to thunniform mode of locomotion as we expected from the traditional classification. While the expected swimming modes correlated with morphological traits, they did not accurately represent the kinematics of BCF locomotion. These results indicate that even fish species differing as substantially in morphology as tuna and eel exhibit statistically similar two-dimensional midline kinematics and point toward unifying locomotor hydrodynamic mechanisms that can serve as the basis for understanding aquatic locomotion and controlling biomimetic aquatic robots.

Many swimming and flying animals are observed to cruise in a narrow range of Strouhal numbers, where the Strouhal number St = 2fA/U is a dimensionless parameter that relates stroke frequency f, amplitude A, and forward speed U. Dolphins, sharks, bony fish, birds, bats, and insects typically cruise in the range 0.2 < St < 0.4, which coincides with the Strouhal number range for maximum efficiency as found by experiments on heaving and pitching airfoils. It has therefore been postulated that natural selection has tuned animals to use this range of Strouhal numbers because it confers high efficiency, but the reason why this is so is still unclear. Here, by using simple scaling arguments, we argue that the Strouhal number for peak efficiency is largely determined by fluid drag on the fins and wings.

Inspired by the relatively simple morphological blueprint provided by batoid fish such as stingrays and skates, we created a biohybrid system that enables an artificial animal—a tissue-engineered ray—to swim and phototactically follow a light cue. By patterning dissociated rat cardiomyocytes on an elastomeric body enclosing a microfabricated gold skeleton, we replicated fish morphology at 1/10 scale and captured basic fin deflection patterns of batoid fish. Optogenetics allows for phototactic guidance, steering, and turning maneuvers. Optical stimulation induced sequential muscle activation via serpentine-patterned muscle circuits, leading to coordinated undulatory swimming. The speed and direction of the ray was controlled by modulating light frequency and by independently eliciting right and left fins, allowing the biohybrid machine to maneuver through an obstacle course.

Fish in schooling formations navigate complex flow fields replete with mechanical energy in the vortex wakes of their companions. Their schooling behavior has been associated with evolutionary advantages including energy savings, yet the underlying physical mechanisms remain unknown. We show that fish can improve their sustained propulsive efficiency by placing themselves in appropriate locations in the wake of other swimmers and intercepting judiciously their shed vortices. This swimming strategy leads to collective energy savings and is revealed through a combination of high-fidelity flow simulations with a deep reinforcement learning (RL) algorithm. The RL algorithm relies on a policy defined by deep, recurrent neural nets, with long–short-term memory cells, that are essential for capturing the unsteadiness of the two-way interactions between the fish and the vortical flow field. Surprisingly, we find that swimming in-line with a leader is not associated with energetic benefits for the follower. Instead, “smart swimmer(s)” place themselves at off-center positions, with respect to the axis of the leader(s) and deform their body to synchronize with the momentum of the oncoming vortices, thus enhancing their swimming efficiency at no cost to the leader(s). The results confirm that fish may harvest energy deposited in vortices and support the conjecture that swimming in formation is energetically advantageous. Moreover, this study demonstrates that deep RL can produce navigation algorithms for complex unsteady and vortical flow fields, with promising implications for energy savings in autonomous robotic swarms.

The anterior body of many fishes is shaped like an airfoil turned on its side. With an oscillating angle to the swimming direction, such an airfoil experiences negative pressure due to both its shape and pitching movements. This negative pressure acts as thrust forces on the anterior body. Here, we apply a high-resolution, pressurebased approach to describe how two fishes, bluegill sunfish (Lepomis macrochirus Rafinesque) and brook trout (Salvelinus fontinalis Mitchill), swimming in the carangiform mode, the most common fish swimming mode, generate thrust on their anterior bodies using leading-edge suction mechanics, much like an airfoil. These mechanics contrast with those previously reported in lampreys— anguilliform swimmers—which produce thrust with negative pressure but do so through undulatory mechanics. The thrust produced on the anterior bodies of these carangiform swimmers through negative pressure comprises 28% of the total thrust produced over the body and caudal fin, substantially decreasing the net drag on the anterior body. On the posterior region, subtle differences in body shape and kinematics allow trout to produce more thrust than bluegill, suggesting that they may swim more effectively. Despite the large phylogenetic distance between these species, and differences near the tail, the pressure profiles around the anterior body are similar. We suggest that such airfoil-like mechanics are highly efficient, because they require very little movement and therefore relatively little active muscular energy, and may be used by a wide range of fishes since many species have appropriately shaped bodies.

High-speed tracking of effortful responses and neuronal activity in rats during a forced swim test identifies medial prefrontal cortex (mPFC) neurons that respond during escape-related swimming but not normal locomotion, and optogenetics shows that mPFC neurons projecting to the brainstem dorsal raphe nucleus, which is implicated in depression, modulate this behavioural response to challenge The neural circuitry of choice Disruption of the prefrontal cortex (PFC) area in the human brain can lead either to impulsive behaviour or to a lack of motivation. This study explores the role of particular populations of PFC neurons in mice during a challenging behavioural situation — the forced swim test. The authors identify neurons that respond during forced swimming, but not during normal locomotion. Using optogenetic manipulation, they show that only the specific population of PFC neurons projecting to the brainstem dorsal raphe nucleus, a region implicated in depression, induces changes in behaviour during forced swimming. These results throw light on the neural circuitry underlying normal and pathological patterns of action selection and motivation in behaviour. The prefrontal cortex (PFC) is thought to participate in high-level control of the generation of behaviours (including the decision to execute actions 1 ); indeed, imaging and lesion studies in human beings have revealed that PFC dysfunction can lead to either impulsive states with increased tendency to initiate action 2 , or to amotivational states characterized by symptoms such as reduced activity, hopelessness and depressed mood 3 . Considering the opposite valence of these two phenotypes as well as the broad complexity of other tasks attributed to PFC, we sought to elucidate the PFC circuitry that favours effortful behavioural responses to challenging situations. Here we develop and use a quantitative method for the continuous assessment and control of active response to a behavioural challenge, synchronized with single-unit electrophysiology and optogenetics in freely moving rats. In recording from the medial PFC (mPFC), we observed that many neurons were not simply movement-related in their spike-firing patterns but instead were selectively modulated from moment to moment, according to the animal’s decision to act in a challenging situation. Surprisingly, we next found that direct activation of principal neurons in the mPFC had no detectable causal effect on this behaviour. We tested whether this behaviour could be causally mediated by only a subclass of mPFC cells defined by specific downstream wiring. Indeed, by leveraging optogenetic projection-targeting to control cells with specific efferent wiring patterns, we found that selective activation of those mPFC cells projecting to the brainstem dorsal raphe nucleus (DRN), a serotonergic nucleus implicated in major depressive disorder 4 , induced a profound, rapid and reversible effect on selection of the active behavioural state. These results may be of importance in understanding the neural circuitry underlying normal and pathological patterns of action selection and motivation in behaviour.

Recent reports have revealed that oligodendrocyte precursor cells (OPCs) are heterogeneous. It remains unclear whether such heterogeneity reflects different subtypes of cells with distinct functions or instead reflects transiently acquired states of cells with the same function. By integrating lineage formation of individual OPC clones, single-cell transcriptomics, calcium imaging and neural activity manipulation, we show that OPCs in the zebrafish spinal cord can be divided into two functionally distinct groups. One subgroup forms elaborate networks of processes and exhibits a high degree of calcium signaling, but infrequently differentiates despite contact with permissive axons. Instead, these OPCs divide in an activity- and calcium-dependent manner to produce another subgroup, with higher process motility and less calcium signaling and that readily differentiates. Our data show that OPC subgroups are functionally diverse in their response to neurons and that activity regulates the proliferation of a subset of OPCs that is distinct from the cells that generate differentiated oligodendrocytes.Oligodendrocyte precursor cells divide or differentiate in response to external stimuli to control their numbers and to form new myelin. Using zebrafish, we show that these two functions are accomplished by distinct subgroups of cells.

The question of how individuals in a population organize when living in groups arises for systems as different as a swarm of microorganisms or a flock of seagulls. The different patterns for moving collectively involve a wide spectrum of reasons, such as evading predators or optimizing food prospection. Also, the schooling pattern has often been associated with an advantage in terms of energy consumption. In this study, we use a popular aquarium fish, the red nose tetra fish, Hemigrammus bleheri, which is known to swim in highly cohesive groups, to analyze the schooling dynamics. In our experiments, fish swim in a shallow-water tunnel with controlled velocity, and stereoscopic video recordings are used to track the 3D positions of each individual in a school, as well as their tail-beating kinematics. Challenging the widespread idea of fish favoring a diamond pattern to swim more efficiently [Weihs D (1973) Nature 241:290–291], we observe that when fish are forced to swim fast—well above their free-swimming typical velocity, and hence in a situation where efficient swimming would be favored—the most frequent configuration is the “phalanx” or “soldier” formation, with all individuals swimming side by side. We explain this observation by considering the advantages of tail-beating synchronization between neighbors, which we have also characterized. Most importantly, we show that schooling is advantageous as compared with swimming alone from an energy-efficiency perspective.