TREBLE: a generalizable framework for high-throughput behavioral analysis

Understanding the relationships between neural activity and behavior represents a critical challenge, one that requires generalizable statistical tools that can capture complex structures within large datasets. We developed Time-REsolved BehavioraL Embedding (TREBLE), a flexible method for analyzing behavioral data from freely moving animals. Using data from synthetic trajectories, fruit flies, and mice we show how TREBLE can capture both continuous and discrete behavioral dynamics, can uncover behavioral variation across individuals, and can detect the effects of optogenetic perturbation in an unbiased fashion. By applying TREBLE to the freely moving mouse, and medial entorhinal cortex (MEC) recordings, we show that nearly all MEC neurons encode information relevant to specific movement patterns, expanding our understanding of how navigation is related to the execution of locomotion. Thus, TREBLE provides a flexible framework for describing the structure of complex behaviors and their relationships to neural activity.

[1]  M. Moser,et al.  Representation of Geometric Borders in the Entorhinal Cortex , 2008, Science.

[2]  Surya Ganguli,et al.  A Multiplexed, Heterogeneous, and Adaptive Code for Navigation in Medial Entorhinal Cortex , 2017, Neuron.

[3]  B. Cheeran,et al.  Inter-individual Variability in Response to Non-invasive Brain Stimulation Paradigms , 2014, Brain Stimulation.

[4]  Adam J. Calhoun,et al.  Unsupervised identification of the internal states that shape natural behavior , 2019, Nature Neuroscience.

[5]  R. Staden A strategy of DNA sequencing employing computer programs. , 1979, Nucleic acids research.

[6]  Torkel Hafting,et al.  Conjunctive Representation of Position, Direction, and Velocity in Entorhinal Cortex , 2006, Science.

[7]  Jamey S. Kain,et al.  Neuronal control of locomotor handedness in Drosophila , 2014, Proceedings of the National Academy of Sciences.

[8]  David Kleinfeld,et al.  Hierarchy of orofacial rhythms revealed through whisking and breathing , 2013, Nature.

[9]  S. Benhamou,et al.  Spatial analysis of animals' movements using a correlated random walk model* , 1988 .

[10]  Román A. Corfas,et al.  Diverse Food-Sensing Neurons Trigger Idiothetic Local Search in Drosophila , 2019, Current Biology.

[11]  Edward S Boyden,et al.  Principles of designing interpretable optogenetic behavior experiments , 2015, Learning & memory.

[12]  David J. Anderson,et al.  Computational Neuroethology: A Call to Action , 2019, Neuron.

[13]  Edvard I. Moser,et al.  Speed cells in the medial entorhinal cortex , 2015, Nature.

[14]  Xin Jin,et al.  Shaping action sequences in basal ganglia circuits , 2015, Current Opinion in Neurobiology.

[15]  Weiyue Li,et al.  Development and Analysis , 2013 .

[16]  Benjamin L de Bivort,et al.  Behavioral idiosyncrasy reveals genetic control of phenotypic variability , 2014, Proceedings of the National Academy of Sciences.

[17]  Manuel Zimmer,et al.  Nested Neuronal Dynamics Orchestrate a Behavioral Hierarchy across Timescales , 2019, Neuron.

[18]  Gordon J. Berman,et al.  Optogenetic dissection of descending behavioral control in Drosophila , 2017, bioRxiv.

[19]  Michael B. Reiser,et al.  Mapping the Neural Substrates of Behavior , 2017, Cell.

[20]  Ryan P. Adams,et al.  Mapping Sub-Second Structure in Mouse Behavior , 2015, Neuron.

[21]  M. Gerstein,et al.  RNA-Seq: a revolutionary tool for transcriptomics , 2009, Nature Reviews Genetics.

[22]  Leland McInnes,et al.  UMAP: Uniform Manifold Approximation and Projection for Dimension Reduction , 2018, ArXiv.

[23]  Michael H. Dickinson,et al.  Diverse food-sensing neurons trigger idiothetic local search in Drosophila , 2018 .

[24]  D. McLean,et al.  trajr: An R package for characterisation of animal trajectories , 2018 .

[25]  M. Orger,et al.  Structure of the Zebrafish Locomotor Repertoire Revealed with Unsupervised Behavioral Clustering , 2018, Current Biology.

[26]  David J. Anderson,et al.  Toward a Science of Computational Ethology , 2014, Neuron.

[27]  Laura J. Grundy,et al.  A dictionary of behavioral motifs reveals clusters of genes affecting Caenorhabditis elegans locomotion , 2012, Proceedings of the National Academy of Sciences.

[28]  Vivek Jayaraman,et al.  Visually Guided Behavior and Optogenetically Induced Learning in Head-Fixed Flies Exploring a Virtual Landscape , 2019, Current Biology.

[29]  Mark D Humphries,et al.  A spiral attractor network drives rhythmic locomotion , 2017, bioRxiv.

[30]  T. Hafting,et al.  Microstructure of a spatial map in the entorhinal cortex , 2005, Nature.

[31]  Thomas R Clandinin,et al.  Dynamic structure of locomotor behavior in walking fruit flies , 2017, eLife.

[32]  Scott W. Linderman,et al.  The Striatum Organizes 3D Behavior via Moment-to-Moment Action Selection , 2018, Cell.

[33]  Adam J. Calhoun,et al.  Quantifying behavior to solve sensorimotor transformations: advances from worms and flies , 2017, Current Opinion in Neurobiology.

[34]  David J. Anderson,et al.  A Brain Module for Scalable Control of Complex, Multi-motor Threat Displays , 2018, Neuron.

[35]  Konrad P. Körding,et al.  The Development and Analysis of Integrated Neuroscience Data , 2016, Front. Comput. Neurosci..

[36]  M. A. MacIver,et al.  Neuroscience Needs Behavior: Correcting a Reductionist Bias , 2017, Neuron.

[37]  Benjamin L. de Bivort,et al.  Ethology as a physical science , 2018, Nature Physics.

[38]  Mark D. Humphries,et al.  Author response: A spiral attractor network drives rhythmic locomotion , 2017 .

[39]  William Bialek,et al.  Mapping the stereotyped behaviour of freely moving fruit flies , 2013, Journal of The Royal Society Interface.

[40]  Jonathan W. Pillow,et al.  Unsupervised identification of the internal states that shape natural behavior , 2019, Nature Neuroscience.