Automatically tracking neurons in a moving and deforming brain

Abstract

Advances in optical neuroimaging techniques now allow neural activity to be recorded with cellular resolution in awake and behaving animals. Brain motion in these recordings pose a unique challenge. The location of individual neurons must be tracked in 3D over time to accurately extract single neuron activity traces. Recordings from small invertebrates like C. elegans are especially challenging because they undergo very large brain motion and deformation during animal movement. Here we present an automated computer vision pipeline to reliably track populations of neurons with single neuron resolution in the brain of a freely moving C. elegans undergoing large motion and deformation. 3D volumetric fluorescent images of the animal's brain are straightened, aligned and registered, and the locations of neurons in the images are found via segmentation. Each neuron is then assigned an identity using a new time-independent machine-learning approach we call Neuron Registration Vector Encoding. In this approach, non-rigid point-set registration is used to match each segmented neuron in each volume with a set of reference volumes taken from throughout the recording. The way each neuron matches with the references defines a feature vector which is clustered to assign an identity to each neuron in each volume. Finally, thin-plate spline interpolation is used to correct errors in segmentation and check consistency of assigned identities. The Neuron Registration Vector Encoding approach proposed here is uniquely well suited for tracking neurons in brains undergoing large deformations. When applied to whole-brain calcium imaging recordings in freely moving C. elegans, this analysis pipeline located 150 neurons for the duration of an 8 minute recording and consistently found more neurons more quickly than manual or semi-automated approaches.

33 pages, 7 figures, code available

References in corpus (3)

• Simultaneous whole-animal 3D-imaging of neuronal activity using light field microscopy
• Whole-brain calcium imaging with cellular resolution in freely behaving C. elegans
• Resolving coiled shapes reveals new reorientation behaviors in C. elegans

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• Correcting motion induced fluorescence artifacts in two-channel neural imaging
• Rapid detection and recognition of whole brain activity in a freely behaving Caenorhabditis elegans
• Robust approximate linear regression without correspondence
• Digging Deeper: Methodologies for High-Content Phenotyping and Knowledge-Abstraction in C. elegans