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175 Janelia Publications

Showing 141-150 of 175 results
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    03/11/22 | Motor cortical output for skilled forelimb movement is selectively distributed across projection neuron classes.
    Park J, Phillips JW, Guo J, Martin KA, Hantman AW, Dudman JT
    Science Advances. 2022 Mar 11;8(10):eabj5167. doi: 10.1126/sciadv.abj5167

    The interaction of descending neocortical outputs and subcortical premotor circuits is critical for shaping skilled movements. Two broad classes of motor cortical output projection neurons provide input to many subcortical motor areas: pyramidal tract (PT) neurons, which project throughout the neuraxis, and intratelencephalic (IT) neurons, which project within the cortex and subcortical striatum. It is unclear whether these classes are functionally in series or whether each class carries distinct components of descending motor control signals. Here, we combine large-scale neural recordings across all layers of motor cortex with cell type-specific perturbations to study cortically dependent mouse motor behaviors: kinematically variable manipulation of a joystick and a kinematically precise reach-to-grasp. We find that striatum-projecting IT neuron activity preferentially represents amplitude, whereas pons-projecting PT neurons preferentially represent the variable direction of forelimb movements. Thus, separable components of descending motor cortical commands are distributed across motor cortical projection cell classes.

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    03/09/22 | Regulation of liver subcellular architecture controls metabolic homeostasis.
    Parlakgül G, Arruda AP, Pang S, Cagampan E, Min N, Güney E, Lee GY, Inouye K, Hess HF, Xu CS, Hotamışlıgil GS
    Nature. 2022 Mar 09;603(7902):736-742. doi: 10.1038/s41586-022-04488-5

    Cells display complex intracellular organization by compartmentalization of metabolic processes into organelles, yet the resolution of these structures in the native tissue context and their functional consequences are not well understood. Here we resolved the three-dimensional structural organization of organelles in large (more than 2.8 × 10 µm) volumes of intact liver tissue (15 partial or full hepatocytes per condition) at high resolution (8 nm isotropic pixel size) using enhanced focused ion beam scanning electron microscopy imaging followed by deep-learning-based automated image segmentation and 3D reconstruction. We also performed a comparative analysis of subcellular structures in liver tissue of lean and obese mice and found substantial alterations, particularly in hepatic endoplasmic reticulum (ER), which undergoes massive structural reorganization characterized by marked disorganization of stacks of ER sheets and predominance of ER tubules. Finally, we demonstrated the functional importance of these structural changes by monitoring the effects of experimental recovery of the subcellular organization on cellular and systemic metabolism. We conclude that the hepatic subcellular organization of the ER architecture are highly dynamic, integrated with the metabolic state and critical for adaptive homeostasis and tissue health.

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    03/07/22 | Neuromuscular embodiment of feedback control elements in Drosophila flight
    Samuel C. Whitehead , Sofia Leone , Theodore Lindsay , Matthew Meiselman , Noah Cowan , Michael Dickinson , Nilay Yapici , David Stern , Troy Shirangi , Itai Cohen
    bioRxiv. 2022 Mar 07:. doi: 10.1101/2022.02.22.481344

    While insects like Drosophila are flying, aerodynamic instabilities require that they make millisecond-timescale 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 muscles system—modulate specific elements of the PI controller: the angular displacement (integral, I) and angular velocity (proportional, P), 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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    03/03/22 | The Consistency of Gastropod Identified Neurons Distinguishes Intra-Individual Plasticity From Inter-Individual Variability in Neural Circuits.
    Tamvacakis AN, Lillvis JL, Sakurai A, Katz PS
    Frontiers in Behavioral Neuroscience. 2022 Mar 03;16:855235. doi: 10.3389/fnbeh.2022.855235

    Gastropod mollusks are known for their large, individually identifiable neurons, which are amenable to long-term intracellular recordings that can be repeated from animal to animal. The constancy of individual neurons can help distinguish state-dependent or temporal variation within an individual from actual variability between individual animals. Investigations into the circuitry underlying rhythmic swimming movements of the gastropod species, and have uncovered intra- and inter-individual variability in synaptic connectivity and serotonergic neuromodulation. has a reliably evoked escape swim behavior that is produced by a central pattern generator (CPG) composed of a small number of identifiable neurons. There is apparent individual variability in some of the connections between neurons that is inconsequential for the production of the swim behavior under normal conditions, but determines whether that individual can swim following a neural lesion. Serotonergic neuromodulation of synaptic strength intrinsic to the CPG creates neural circuit plasticity within an individual and contributes to reorganization of the network during recovery from injury and during learning. In , variability over time in the modulatory actions of serotonin and in expression of serotonin receptor genes in an identified neuron directly reflects variation in swimming behavior. Tracking behavior and electrophysiology over hours to days was necessary to identify the functional consequences of these intra-individual, time-dependent variations. This work demonstrates the importance of unambiguous neuron identification, properly assessing the animal and network states, and tracking behavior and physiology over time to distinguish plasticity within the same animal at different times from variability across individual animals.

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    02/28/22 | Melding Synthetic Molecules and Genetically Encoded Proteins to Forge New Tools for Neuroscience.
    Kumar P, Lavis LD
    Annual Review of Neuroscience. 2022 Feb 28:. doi: 10.1146/annurev-neuro-110520-030031

    Unraveling the complexity of the brain requires sophisticated methods to probe and perturb neurobiological processes with high spatiotemporal control. The field of chemical biology has produced general strategies to combine the molecular specificity of small-molecule tools with the cellular specificity of genetically encoded reagents. Here, we survey the application, refinement, and extension of these hybrid small-molecule:protein methods to problems in neuroscience, which yields powerful reagents to precisely measure and manipulate neural systems. Expected final online publication date for the , Volume 45 is July 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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    02/28/22 | Melding Synthetic Molecules and Genetically Encoded Proteins to Forge New Tools for Neuroscience.
    Kumar P, Lavis LD
    Annual Review Neuroscience. 2022 Feb 28:. doi: 10.1146/annurev-neuro-110520-030031

    Unraveling the complexity of the brain requires sophisticated methods to probe and perturb neurobiological processes with high spatiotemporal control. The field of chemical biology has produced general strategies to combine the molecular specificity of small-molecule tools with the cellular specificity of genetically encoded reagents. Here, we survey the application, refinement, and extension of these hybrid small-molecule:protein methods to problems in neuroscience, which yields powerful reagents to precisely measure and manipulate neural systems. Expected final online publication date for the , Volume 45 is July 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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    02/25/22 | Online learning for orientation estimation during translation in an insect ring attractor network.
    Robinson BS, Norman-Tenazas R, Cervantes M, Symonette D, Johnson EC, Joyce J, Rivlin PK, Hwang G, Zhang K, Gray-Roncal W
    Scientific Reports. 2022 Feb 25;12(1):3210. doi: 10.1038/s41598-022-05798-4

    Insect neural systems are a promising source of inspiration for new navigation algorithms, especially on low size, weight, and power platforms. There have been unprecedented recent neuroscience breakthroughs with Drosophila in behavioral and neural imaging experiments as well as the mapping of detailed connectivity of neural structures. General mechanisms for learning orientation in the central complex (CX) of Drosophila have been investigated previously; however, it is unclear how these underlying mechanisms extend to cases where there is translation through an environment (beyond only rotation), which is critical for navigation in robotic systems. Here, we develop a CX neural connectivity-constrained model that performs sensor fusion, as well as unsupervised learning of visual features for path integration; we demonstrate the viability of this circuit for use in robotic systems in simulated and physical environments. Furthermore, we propose a theoretical understanding of how distributed online unsupervised network weight modification can be leveraged for learning in a trajectory through an environment by minimizing orientation estimation error. Overall, our results may enable a new class of CX-derived low power robotic navigation algorithms and lead to testable predictions to inform future neuroscience experiments.

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    02/24/22 | Neuromuscular embodiment of feedback control elements in Drosophila flight.
    Samuel C Whitehead , Sofia Leone , Theodore Lindsay , Matthew R Meiselman , Noah Cowan , Michael H Dickinson , Nilay Yapici , David Stern , Troy Shirangi , Itai Cohen
    bioRxiv. 2022 Feb 24:. doi: 10.1101/2022.02.22.481344

    While insects like Drosophila are flying, aerodynamic instabilities require that they make millisecond-timescale 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 muscles system—modulate specific elements of the PI controller: the angular displacement (integral, I) and angular velocity (proportional, P), 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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    02/23/22 | The importance of accounting for movement when relating neuronal activity to sensory and cognitive processes.
    Edward Zagha , Jeffrey C Erlich , Soohyun Lee , Gyorgy Lur , Daniel H O'Connor , Nicholas A Steinmetz , Carsen Stringer , Hongdian Yang
    Journal of Neuroscience: The Official Journal of the Society for Neuroscience. 2022 Feb 23;42(8):1375-1382. doi: 10.1523/JNEUROSCI.1919-21.2021

    A surprising finding of recent studies in mouse is the dominance of widespread movement-related activity throughout the brain, including in early sensory areas. In awake subjects, failing to account for movement risks misattributing movement-related activity to other (e.g., sensory or cognitive) processes. In this article, we 1) review task designs for separating task-related and movement-related activity, 2) review three 'case studies' in which not considering movement would have resulted in critically different interpretations of neuronal function, and 3) discuss functional couplings that may prevent us from ever fully isolating sensory, motor, and cognitive-related activity. Our main thesis is that neural signals related to movement are ubiquitous, and therefore ought to be considered first and foremost when attempting to correlate neuronal activity with task-related processes.

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    Romani LabSvoboda Lab
    02/22/22 | Neural Algorithms and Circuits for Motor Planning.
    Inagaki HK, Chen S, Daie K, Finklestein A, Fontolan L, Romani S, Svoboda K
    Annual Reviews Neuroscience. 2022 Feb 22:. doi: 10.1146/annurev-neuro-092021-121730

    The brain plans and executes volitional movements. The underlying patterns of neural population activity have been explored in the context of movements of the eyes, limbs, tongue, and head in nonhuman primates and rodents. How do networks of neurons produce the slow neural dynamics that prepare specific movements and the fast dynamics that ultimately initiate these movements? Recent work exploits rapid and calibrated perturbations of neural activity to test specific dynamical systems models that are capable of producing the observed neural activity. These joint experimental and computational studies show that cortical dynamics during motor planning reflect fixed points of neural activity (attractors). Subcortical control signals reshape and move attractors over multiple timescales, causing commitment to specific actions and rapid transitions to movement execution. Experiments in rodents are beginning to reveal how these algorithms are implemented at the level of brain-wide neural circuits. Expected final online publication date for the , Volume 45 is July 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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