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621 results on '"Jessell, Thomas M."'

2. Simultaneous Denoising, Deconvolution, and Demixing of Calcium Imaging Data

Author

Pnevmatikakis, Eftychios A, Soudry, Daniel, Gao, Yuanjun, Machado, Timothy A, Merel, Josh, Pfau, David, Reardon, Thomas, Mu, Yu, Lacefield, Clay, Yang, Weijian, Ahrens, Misha, Bruno, Randy, Jessell, Thomas M, Peterka, Darcy S, Yuste, Rafael, and Paninski, Liam

Subjects
Biomedical and Clinical Sciences, Neurosciences, Bioengineering, Underpinning research, 1.1 Normal biological development and functioning, Neurological, Action Potentials, Animals, Calcium, Dendrites, Fluorescent Dyes, Mice, Mice, Inbred C57BL, Microscopy, Fluorescence, Neurons, Statistics as Topic, Psychology, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

We present a modular approach for analyzing calcium imaging recordings of large neuronal ensembles. Our goal is to simultaneously identify the locations of the neurons, demix spatially overlapping components, and denoise and deconvolve the spiking activity from the slow dynamics of the calcium indicator. Our approach relies on a constrained nonnegative matrix factorization that expresses the spatiotemporal fluorescence activity as the product of a spatial matrix that encodes the spatial footprint of each neuron in the optical field and a temporal matrix that characterizes the calcium concentration of each neuron over time. This framework is combined with a novel constrained deconvolution approach that extracts estimates of neural activity from fluorescence traces, to create a spatiotemporal processing algorithm that requires minimal parameter tuning. We demonstrate the general applicability of our method by applying it to in vitro and in vivo multi-neuronal imaging data, whole-brain light-sheet imaging data, and dendritic imaging data.

Published
2016

42. Presynaptic inhibition of spinal sensory feedback ensures smooth movement

Author

Fink, Andrew J.P., Croce, Katherine R., Huang, Z. Josh, Abbott, L.F., Jessell, Thomas M., and Azim, Eiman

Subjects
Physiological research, Animal locomotion -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The precision of skilled movement depends on sensory feedback and its refinement by local inhibitory microcircuits. One specialized set of spinal GABAergic interneurons forms axo--axonic contacts with the central terminals of sensory afferents, exerting presynaptic inhibitory control over sensory--motor transmission. The inability to achieve selective access to the GABAergic neurons responsible for this unorthodox inhibitory mechanism has left unresolved the contribution of presynaptic inhibition to motor behaviour. We used Gad2 as a genetic entry point to manipulate the interneurons that contact sensory terminals, and show that activation of these interneurons in mice elicits the defining physiological characteristics of presynaptic inhibition. Selective genetic ablation of Gad2--expressing interneurons severely perturbs goal--directed reaching movements, uncovering a pronounced and stereotypic forelimb motor oscillation, the core features of which are captured by modelling the consequences of sensory feedback at high gain. Our findings define the neural substrate of a genetically hardwired gain control system crucial for the smooth execution of movement., Animals execute skilled limb movements with seemingly effortless precision, belying an elaborate series of neural transformations that direct each motor act. Spinal motor output relies on local inhibitory interneurons that [...]

Published
2014

43. Skilled reaching relies on a V2a propriospinal internal copy circuit

Author

Azim, Eiman, Jiang, Juan, Alstermark, Bror, and Jessell, Thomas M.

Subjects
Extremities (Anatomy) -- Physiological aspects, Neurons -- Physiological aspects, Human mechanics -- Research, Zoological research, Mammals -- Physiological aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The precision of skilled forelimb movement has long been presumed to rely on rapid feedback corrections triggered by internally directed copies of outgoing motor commands, but the functional relevance of inferred internal copy circuits has remained unclear. One class of spinal interneurons implicated in the control of mammalian forelimb movement, cervical propriospinal neurons (PNs), has the potential to convey an internal copy of premotor signals through dual innervation of forelimb-innervating motor neurons and precerebellar neurons of the lateral reticular nucleus. Here we examine whether the PN internal copy pathway functions in the control of goal-directed reaching. In mice, PNs include a genetically accessible subpopulation of cervical V2a interneurons, and their targeted ablation perturbs reaching while leaving intact other elements of forelimb movement. Moreover, optogenetic activation of the PN internal copy branch recruits a rapid cerebellar feedback loop that modulates forelimb motor neuron activity and severely disrupts reaching kinematics. Our findings implicate V2a PNs as the focus of an internal copy pathway assigned to the rapid updating of motor output during reaching behaviour. Cervical propriospinal neurons (PNs) form a genetically accessible subclass of V2a interneurons that convey both premotor output and precerebellar copy signals; their ablation in mice impairs reaching movements selectively, and activation of their internal copy projection recruits a rapid cerebellar feedback loop that modulates forelimb movement. Brainstem circuits controlling precision movement Two papers published in this issue of Nature address a long-standing puzzle in mammalian motor control -- the organization and function of circuits between the brain and spinal cord that control motor movements such as reaching. Thomas Jessell and colleagues investigate a class of mouse spinal interneurons known in other species to be involved in fine forelimb movements. They show that in mouse, these neurons have appropriate anatomical innervation to carry both motor commands and an internal copy signal, and ablation of these neurons impairs reaching movements. Furthermore, optogenetic activation of the ascending branch recruits a cerebellar circuit, and also disrupts reaching movements. These findings implicate these neurons as part of an internal copy pathway for rapid updating of motor output during reaching. Silvia Arber and colleagues use a combination of viral tracing and genetics to characterize the diversity of neurons projecting from mouse brainstem to motor neurons that control limb movements. They discover that one region in particular, the ventral medullary reticular formation or MdV, is functionally specialized for forelimb motor control. Neurons here specifically target forelimb neurons and are recruited during motor tasks, and inactivation of these neurons impairs fine movements., Author(s): Eiman Azim [sup.1] , Juan Jiang [sup.2] , Bror Alstermark [sup.2] , Thomas M. Jessell [sup.1] Author Affiliations: (1) Departments of Neuroscience and Biochemistry and Molecular Biophysics, Howard Hughes [...]

Published
2014
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