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56 Publications

Showing 41-50 of 56 results
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    12/30/14 | Light-sheet imaging for systems neuroscience.
    Keller PJ, Ahrens MB, Freeman J
    Nature Methods. 2014 Dec 30;12(1):27-9. doi: 10.1038/nmeth.3214

    Developments in electrical and optical recording technology are scaling up the size of neuronal populations that can be monitored simultaneously. Light-sheet imaging is rapidly gaining traction as a method for optically interrogating activity in large networks and presents both opportunities and challenges for understanding circuit function.

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    Ahrens LabLooger LabKeller LabFreeman Lab
    07/27/14 | Light-sheet functional imaging in fictively behaving zebrafish.
    Vladimirov N, Mu Y, Kawashima T, Bennett DV, Yang C, Looger LL, Keller PJ, Freeman J, Ahrens MB
    Nature Methods. 2014 Jul 27;11(9):883-4. doi: 10.1038/nmeth.3040

    The processing of sensory input and the generation of behavior involves large networks of neurons, which necessitates new technology for recording from many neurons in behaving animals. In the larval zebrafish, light-sheet microscopy can be used to record the activity of almost all neurons in the brain simultaneously at single-cell resolution. Existing implementations, however, cannot be combined with visually driven behavior because the light sheet scans over the eye, interfering with presentation of controlled visual stimuli. Here we describe a system that overcomes the confounding eye stimulation through the use of two light sheets and combines whole-brain light-sheet imaging with virtual reality for fictively behaving larval zebrafish.

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    Looger LabAhrens LabFreeman LabSvoboda Lab
    07/27/14 | Mapping brain activity at scale with cluster computing.
    Freeman J, Vladimirov N, Kawashima T, Mu Y, Sofroniew NJ, Bennett DV, Rosen J, Yang C, Looger LL, Ahrens MB
    Nature Methods. 2014 Jul 27;11(9):941-950. doi: 10.1038/nmeth.3041

    Understanding brain function requires monitoring and interpreting the activity of large networks of neurons during behavior. Advances in recording technology are greatly increasing the size and complexity of neural data. Analyzing such data will pose a fundamental bottleneck for neuroscience. We present a library of analytical tools called Thunder built on the open-source Apache Spark platform for large-scale distributed computing. The library implements a variety of univariate and multivariate analyses with a modular, extendable structure well-suited to interactive exploration and analysis development. We demonstrate how these analyses find structure in large-scale neural data, including whole-brain light-sheet imaging data from fictively behaving larval zebrafish, and two-photon imaging data from behaving mouse. The analyses relate neuronal responses to sensory input and behavior, run in minutes or less and can be used on a private cluster or in the cloud. Our open-source framework thus holds promise for turning brain activity mapping efforts into biological insights.

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    08/19/13 | Spinal projection neurons control turning behaviors in zebrafish.
    Huang K, Ahrens MB, Dunn TW, Engert F
    Current Biology. 2013 Aug 19;23(16):1566-73. doi: 10.1016/j.cub.2013.06.044

    Discrete populations of brainstem spinal projection neurons (SPNs) have been shown to exhibit behavior-specific responses during locomotion [1-9], suggesting that separate descending pathways, each dedicated to a specific behavior, control locomotion. In an alternative model, a large variety of motor outputs could be generated from different combinations of a small number of basic motor pathways. We examined this possibility by studying the precise role of ventromedially located hindbrain SPNs (vSPNs) in generating turning behaviors. We found that unilateral laser ablation of vSPNs reduces the tail deflection and cycle period specifically during the first undulation cycle of a swim bout, whereas later tail movements are unaffected. This holds true during phototaxic [10], optomotor [11], dark-flash-induced [12], and spontaneous turns [13], suggesting a universal role of these neurons in controlling turning behaviors. Importantly, we found that the ablation not only abolishes turns but also results in a dramatic increase in the number of forward swims, suggesting that these neurons transform forward swims into turns by introducing turning kinematics into a basic motor pattern of symmetric tail undulations. Finally, we show that vSPN activity is direction specific and graded by turning angle. Together, these results provide a clear example of how a specific motor pattern can be transformed into different behavioral events by the graded activation of a small set of SPNs.

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    06/06/13 | Two-photon calcium imaging during fictive navigation in virtual environments.
    Ahrens MB, Huang KH, Narayan S, Mensh BD, Engert F
    Frontiers in Neural Circuits. 2013 Jun 6;7:104. doi: 10.3389/fncir.2013.00104 *equal contribution

    A full understanding of nervous system function requires recording from large populations of neurons during naturalistic behaviors. Here we enable paralyzed larval zebrafish to fictively navigate two-dimensional virtual environments while we record optically from many neurons with two-photon imaging. Electrical recordings from motor nerves in the tail are decoded into intended forward swims and turns, which are used to update a virtual environment displayed underneath the fish. Several behavioral features-such as turning responses to whole-field motion and dark avoidance-are well-replicated in this virtual setting. We readily observed neuronal populations in the hindbrain with laterally selective responses that correlated with right or left optomotor behavior. We also observed neurons in the habenula, pallium, and midbrain with response properties specific to environmental features. Beyond single-cell correlations, the classification of network activity in such virtual settings promises to reveal principles of brainwide neural dynamics during behavior.

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    05/01/13 | Whole-brain functional imaging at cellular resolution using light-sheet microscopy.
    Ahrens MB, Orger MB, Robson DN, Li JM, Keller PJ
    Nature Methods. 2013 May;10(5):413-20. doi: 10.1038/nmeth.2434

    Brain function relies on communication between large populations of neurons across multiple brain areas, a full understanding of which would require knowledge of the time-varying activity of all neurons in the central nervous system. Here we use light-sheet microscopy to record activity, reported through the genetically encoded calcium indicator GCaMP5G, from the entire volume of the brain of the larval zebrafish in vivo at 0.8 Hz, capturing more than 80% of all neurons at single-cell resolution. Demonstrating how this technique can be used to reveal functionally defined circuits across the brain, we identify two populations of neurons with correlated activity patterns. One circuit consists of hindbrain neurons functionally coupled to spinal cord neuropil. The other consists of an anatomically symmetric population in the anterior hindbrain, with activity in the left and right halves oscillating in antiphase, on a timescale of 20 s, and coupled to equally slow oscillations in the inferior olive.

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    02/27/13 | Identification of nonvisual photomotor response cells in the vertebrate hindbrain.
    Kokel D, Dunn TW, Ahrens MB, Alshut R, Cheung CY, Saint-Amant L, Bruni G, Mateus R, van Ham TJ, Shiraki T, Fukada Y, Kojima D, Yeh JJ, Mikut R, von Lintig J, Engert F, Peters RT
    The Journal of Neuroscience. 2013 Feb 27;33(9):3834-43. doi: 10.1523/JNEUROSCI.3689-12.2013

    Nonvisual photosensation enables animals to sense light without sight. However, the cellular and molecular mechanisms of nonvisual photobehaviors are poorly understood, especially in vertebrate animals. Here, we describe the photomotor response (PMR), a robust and reproducible series of motor behaviors in zebrafish that is elicited by visual wavelengths of light but does not require the eyes, pineal gland, or other canonical deep-brain photoreceptive organs. Unlike the relatively slow effects of canonical nonvisual pathways, motor circuits are strongly and quickly (seconds) recruited during the PMR behavior. We find that the hindbrain is both necessary and sufficient to drive these behaviors. Using in vivo calcium imaging, we identify a discrete set of neurons within the hindbrain whose responses to light mirror the PMR behavior. Pharmacological inhibition of the visual cycle blocks PMR behaviors, suggesting that opsin-based photoreceptors control this behavior. These data represent the first known light-sensing circuit in the vertebrate hindbrain.

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    02/01/13 | Optogenetics in a transparent animal: circuit function in the larval zebrafish.
    Portugues R, Severi KE, Wyart C, Ahrens MB
    Current Opinion in Neurobiology. 2013 Feb;23(1):119-26. doi: 10.1016/j.conb.2012.11.001

    Optogenetic tools can be used to manipulate neuronal activity in a reversible and specific manner. In recent years, such methods have been applied to uncover causal relationships between activity in specified neuronal circuits and behavior in the larval zebrafish. In this small, transparent, genetic model organism, noninvasive manipulation and monitoring of neuronal activity with light is possible throughout the nervous system. Here we review recent work in which these new tools have been applied to zebrafish, and discuss some of the existing challenges of these approaches.

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    05/24/12 | Brain-wide neuronal dynamics during motor adaptation in zebrafish.
    Ahrens MB, Li JM, Orger MB, Robson DN, Schier AF, Engert F, Portugues R
    Nature. 2012 May 24;485(7399):471-7. doi: 10.1038/nature11057

    A fundamental question in neuroscience is how entire neural circuits generate behaviour and adapt it to changes in sensory feedback. Here we use two-photon calcium imaging to record the activity of large populations of neurons at the cellular level, throughout the brain of larval zebrafish expressing a genetically encoded calcium sensor, while the paralysed animals interact fictively with a virtual environment and rapidly adapt their motor output to changes in visual feedback. We decompose the network dynamics involved in adaptive locomotion into four types of neuronal response properties, and provide anatomical maps of the corresponding sites. A subset of these signals occurred during behavioural adjustments and are candidates for the functional elements that drive motor learning. Lesions to the inferior olive indicate a specific functional role for olivocerebellar circuitry in adaptive locomotion. This study enables the analysis of brain-wide dynamics at single-cell resolution during behaviour.

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    02/08/11 | Observers exploit stochastic models of sensory change to help judge the passage of time.
    Ahrens MB, Sahani M
    Current Biology. 2011 Feb 8;21(3):200-6. doi: 10.1016/j.cub.2010.12.043

    Sensory stimulation can systematically bias the perceived passage of time, but why and how this happens is mysterious. In this report, we provide evidence that such biases may ultimately derive from an innate and adaptive use of stochastically evolving dynamic stimuli to help refine estimates derived from internal timekeeping mechanisms. A simplified statistical model based on probabilistic expectations of stimulus change derived from the second-order temporal statistics of the natural environment makes three predictions. First, random noise-like stimuli whose statistics violate natural expectations should induce timing bias. Second, a previously unexplored obverse of this effect is that similar noise stimuli with natural statistics should reduce the variability of timing estimates. Finally, this reduction in variability should scale with the interval being timed, so as to preserve the overall Weber law of interval timing. All three predictions are borne out experimentally. Thus, in the context of our novel theoretical framework, these results suggest that observers routinely rely on sensory input to augment their sense of the passage of time, through a process of Bayesian inference based on expectations of change in the natural environment.

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