title: Scalable Semisupervised Functional Neurocartography Reveals Canonical Neurons in Behavioral Networks.
abstract: Large-scale data collection efforts to map the brain are underway at multiple spatial and temporal scales, but all face fundamental problems posed by high-dimensional data and intersubject variability. Even seemingly simple problems, such as identifying a neuron/brain region across animals/subjects, become exponentially more difficult in high dimensions, such as recognizing dozens of neurons/brain regions simultaneously. We present a framework and tools for functional neurocartography-the large-scale mapping of neural activity during behavioral states. Using a voltage-sensitive dye (VSD), we imaged the multifunctional responses of hundreds of leech neurons during several behaviors to identify and functionally map homologous neurons. We extracted simple features from each of these behaviors and combined them with anatomical features to create a rich medium-dimensional feature space. This enabled us to use machine learning techniques and visualizations to characterize and account for intersubject variability, piece together a canonical atlas of neural activity, and identify two behavioral networks. We identified 39 neurons (18 pairs, 3 unpaired) as part of a canonical swim network and 17 neurons (8 pairs, 1 unpaired) involved in a partially overlapping preparatory network. All neurons in the preparatory network rapidly depolarized at the onsets of each behavior, suggesting that it is part of a dedicated rapid-response network. This network is likely mediated by the S cell, and we referenced VSD recordings to an activity atlas to identify multiple cells of interest simultaneously in real time for further experiments. We targeted and electrophysiologically verified several neurons in the swim network and further showed that the S cell is presynaptic to multiple neurons in the preparatory network. This study illustrates the basic framework to map neural activity in high dimensions with large-scale recordings and how to extract the rich information necessary to perform analyses in light of intersubject variability.
authors.affiliation: Neurosciences Graduate Program, University of California San Diego, La Jolla, CA 92093, U.S.A. paxon.frady@gmail.com.
authors.forename: E Paxon
authors.initials: EP
authors.lastname: Frady
authors.affiliation: Microsoft Research, Redmond, WA 98052, U.S.A. akapoor@microsoft.com.
authors.forename: Ashish
authors.initials: A
authors.lastname: Kapoor
authors.affiliation: Microsoft Research, Redmond, WA 98052, U.S.A. horvitz@microsoft.com.
authors.forename: Eric
authors.initials: E
authors.lastname: Horvitz
authors.affiliation: Department of Biological Sciences, University of California San Diego, La Jolla, CA 92093, U.S.A. wkristan@ucsd.edu.
authors.forename: William B
authors.initials: WB
authors.lastname: Kristan
mesh_terms: D000818:Animals; D001921:Brain; D001931:Brain Mapping; D006801:Humans; D009474:Neurons