RESUMEN
Precise tongue control is necessary for drinking, eating and vocalizing1-3. However, because tongue movements are fast and difficult to resolve, neural control of lingual kinematics remains poorly understood. Here we combine kilohertz-frame-rate imaging and a deep-learning-based neural network to resolve 3D tongue kinematics in mice drinking from a water spout. Successful licks required corrective submovements that-similar to online corrections during primate reaches4-11-occurred after the tongue missed unseen, distant or displaced targets. Photoinhibition of anterolateral motor cortex impaired corrections, which resulted in hypometric licks that missed the spout. Neural activity in anterolateral motor cortex reflected upcoming, ongoing and past corrective submovements, as well as errors in predicted spout contact. Although less than a tenth of a second in duration, a single mouse lick exhibits the hallmarks of online motor control associated with a primate reach, including cortex-dependent corrections after misses.
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Adaptación Fisiológica , Atención , Ingestión de Líquidos , Corteza Motora/fisiología , Desempeño Psicomotor/fisiología , Lengua/fisiología , Animales , Fenómenos Biomecánicos , Aprendizaje Profundo , Masculino , Ratones , Tiempo de Reacción , AguaRESUMEN
Holding still and aiming reaches to spatial targets may depend on distinct neural circuits. Using automated homecage training and a sensitive joystick, we trained freely-moving mice to contact a joystick, hold their forelimb still, and then reach to rewarded target locations. Mice learned the task by initiating forelimb sequences with clearly resolved submillimeter-scale micromovements followed by millimeter-scale reaches to learned spatial targets. Hundreds of thousands of trajectories were decomposed into millions of kinematic submovements, while photoinhibition was used to test roles of motor cortical areas. Inactivation of both caudal and rostral forelimb areas preserved the ability to produce aimed reaches, but reduced reach speed. Inactivation specifically of contralateral caudal forelimb area (CFA) additionally impaired the ability to aim corrective submovements to remembered locations following target undershoots. Our findings show that motor cortical inactivations reduce the gain of forelimb movements but that inactivation specifically of contralateral CFA impairs corrective movements important for reaching a target location.
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An obstacle to understanding neural mechanisms of movement is the complex, distributed nature of the mammalian motor system. Here we present a novel behavioral paradigm for high-throughput dissection of neural circuits underlying mouse forelimb control. Custom touch-sensing joysticks were used to quantify mouse forelimb trajectories with micron-millisecond spatiotemporal resolution. Joysticks were integrated into computer-controlled, rack-mountable home cages, enabling batches of mice to be trained in parallel. Closed loop behavioral analysis enabled online control of reward delivery for automated training. We used this system to show that mice can learn, with no human handling, a direction-specific hold-still center-out reach task in which a mouse first held its right forepaw still before reaching out to learned spatial targets. Stabilogram diffusion analysis of submillimeter-scale micromovements produced during the hold demonstrate that an active control process, akin to upright balance, was implemented to maintain forepaw stability. Trajectory decomposition methods, previously used in primates, were used to segment hundreds of thousands of forelimb trajectories into millions of constituent kinematic primitives. This system enables rapid dissection of neural circuits for controlling motion primitives from which forelimb sequences are built. NEW & NOTEWORTHY A novel joystick design resolves mouse forelimb kinematics with micron-millisecond precision. Home cage training is used to train mice in a hold-still center-out reach task. Analytical methods, previously used in primates, are used to decompose mouse forelimb trajectories into kinematic primitives.
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Miembro Anterior/fisiología , Aprendizaje , Movimiento , Conducta Espacial , Animales , Automatización/métodos , Fenómenos Biomecánicos , Miembro Anterior/inervación , Masculino , Ratones , Ratones Endogámicos C57BL , Neurofisiología/métodosRESUMEN
Flapping insect flight is a complex and beautiful phenomenon that relies on fast, active control mechanisms to counter aerodynamic instability. To directly investigate how freely flying Drosophila melanogaster control their body pitch angle against such instability, we perturbed them using impulsive mechanical torques and filmed their corrective maneuvers with high-speed video. Combining experimental observations and numerical simulation, we found that flies correct for pitch deflections of up to 40 deg in 29±8â ms by bilaterally modulating their wings' front-most stroke angle in a manner well described by a linear proportional-integral (PI) controller. Flies initiate this corrective process only 10±2â ms after the perturbation onset, indicating that pitch stabilization involves a fast reflex response. Remarkably, flies can also correct for very large-amplitude pitch perturbations--greater than 150 deg--providing a regime in which to probe the limits of the linear-response framework. Together with previous studies regarding yaw and roll control, our results on pitch show that flies' stabilization of each of these body angles is consistent with PI control.
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Drosophila melanogaster/fisiología , Vuelo Animal/fisiología , Alas de Animales/fisiología , Animales , Fenómenos Biomecánicos , TorqueRESUMEN
Similar to other animals, the fly, Drosophila melanogaster, changes its foraging strategy from exploration to exploitation upon encountering a nutrient-rich food source. However, the impact of metabolic state or taste/nutrient value on exploration vs. exploitation decisions in flies is poorly understood. Here, we developed a one-source foraging assay that uses automated video tracking coupled with high-resolution measurements of food ingestion to investigate the behavioral variables flies use when foraging for food with different taste/caloric values and when in different metabolic states. We found that flies alter their foraging and ingestive behaviors based on their hunger state and the concentration of the sucrose solution. Interestingly, sugar-blind flies did not transition from exploration to exploitation upon finding a high-concentration sucrose solution, suggesting that taste sensory input, as opposed to post-ingestive nutrient feedback, plays a crucial role in determining the foraging decisions of flies. Using a Generalized Linear Model (GLM), we showed that hunger state and sugar volume ingested, but not the nutrient or taste value of the food, influence flies' radial distance to the food source, a strong indicator of exploitation. Our behavioral paradigm and theoretical framework offer a promising avenue for investigating the neural mechanisms underlying state and value-based foraging decisions in flies, setting the stage for systematically identifying the neuronal circuits that drive these behaviors.
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To perform most behaviors, animals must send commands from higher-order processing centers in the brain to premotor circuits that reside in ganglia distinct from the brain, such as the mammalian spinal cord or insect ventral nerve cord. How these circuits are functionally organized to generate the great diversity of animal behavior remains unclear. An important first step in unraveling the organization of premotor circuits is to identify their constituent cell types and create tools to monitor and manipulate these with high specificity to assess their function. This is possible in the tractable ventral nerve cord of the fly. To generate such a toolkit, we used a combinatorial genetic technique (split-GAL4) to create 195 sparse driver lines targeting 198 individual cell types in the ventral nerve cord. These included wing and haltere motoneurons, modulatory neurons, and interneurons. Using a combination of behavioral, developmental, and anatomical analyses, we systematically characterized the cell types targeted in our collection. Taken together, the resources and results presented here form a powerful toolkit for future investigations of neural circuits and connectivity of premotor circuits while linking them to behavioral outputs.
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While insects such as Drosophila are flying, aerodynamic instabilities require that they make millisecond time scale adjustments to their wing motion to stay aloft and on course. These stabilization reflexes can be modeled as a proportional-integral (PI) controller; however, it is unclear how such control might be instantiated in insects at the level of muscles and neurons. Here, we show that the b1 and b2 motor units-prominent components of the fly's steering muscle system-modulate specific elements of the PI controller: the angular displacement (integral) and angular velocity (proportional), respectively. Moreover, these effects are observed only during the stabilization of pitch. Our results provide evidence for an organizational principle in which each muscle contributes to a specific functional role in flight control, a finding that highlights the power of using top-down behavioral modeling to guide bottom-up cellular manipulation studies.
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Across animal species, meals are terminated after ingestion of large food volumes, yet underlying mechanosensory receptors have so far remained elusive. Here, we identify an essential role for Drosophila Piezo in volume-based control of meal size. We discover a rare population of fly neurons that express Piezo, innervate the anterior gut and crop (a food reservoir organ), and respond to tissue distension in a Piezo-dependent manner. Activating Piezo neurons decreases appetite, while Piezo knockout and Piezo neuron silencing cause gut bloating and increase both food consumption and body weight. These studies reveal that disrupting gut distension receptors changes feeding patterns and identify a key role for Drosophila Piezo in internal organ mechanosensation.
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Proteínas de Drosophila/genética , Drosophila melanogaster/fisiología , Canales Iónicos/genética , Mecanotransducción Celular/genética , Animales , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Conducta Alimentaria/fisiología , Femenino , Tracto Gastrointestinal/fisiología , Canales Iónicos/metabolismo , Masculino , Células Receptoras Sensoriales/fisiologíaRESUMEN
Lipid phase heterogeneity in the plasma membrane is thought to be crucial for many aspects of cell signaling, but the physical basis of participating membrane domains such as "lipid rafts" remains controversial. Here we consider a lattice model yielding a phase diagram that includes several states proposed to be relevant for the cell membrane, including microemulsion-which can be related to membrane curvature-and Ising critical behavior. Using a neural-network-based machine learning approach, we compute the full phase diagram of this lattice model. We analyze selected regions of this phase diagram in the context of a signaling initiation event in mast cells: recruitment of the membrane-anchored tyrosine kinase Lyn to a cluster of transmembrane IgE-FcεRI receptors. We find that model membrane systems in microemulsion and Ising critical states can mediate roughly equal levels of kinase recruitment (binding energy ⼠-0.6 kB T), whereas a membrane near a tricritical point can mediate a much stronger kinase recruitment (-1.7 kB T). By comparing several models for lipid heterogeneity within a single theoretical framework, this work points to testable differences between existing models. We also suggest the tricritical point as a new possibility for the basis of membrane domains that facilitate preferential partitioning of signaling components.