NeuroPAL: A Multicolor Atlas for Whole-Brain Neuronal Identification in C. elegans

January 7, 2021

Comprehensively resolving neuronal identities in whole-brain images is a major challenge. We achieve this in C. elegans by engineering a multicolor transgene called NeuroPAL (a neuronal polychromatic atlas of landmarks). NeuroPAL worms share a stereotypical multicolor fluorescence map for the entire hermaphrodite nervous system that resolves all neuronal identities. Neurons labeled with NeuroPAL do not exhibit fluorescence in the green, cyan, or yellow emission channels, allowing the transgene to be used with numerous reporters of gene expression or neuronal dynamics. We showcase three applications that leverage NeuroPAL for nervous-system-wide neuronal identification. First, we determine the brainwide expression patterns of all metabotropic receptors for acetylcholine, GABA, and glutamate, completing a map of this communication network. Second, we uncover changes in cell fate caused by transcription factor mutations. Third, we record brainwide activity in response to attractive and repulsive chemosensory cues, characterizing multimodal coding for these stimuli.

-Eviatar Yemini , Albert Lin , Amin Nejatbakhsh , Erdem Varol , Ruoxi Sun , Gonzalo E Mena , Aravinthan D T Samuel , Liam Paninski , Vivek Venkatachalam , Oliver Hobert 

Distinct temporal difference error signals in dopamine axons in three regions of the striatum in a decision-making task

December 21, 2020

Different regions of the striatum regulate different types of behavior. However, how dopamine signals differ across striatal regions and how dopamine regulates different behaviors remain unclear. Here, we compared dopamine axon activity in the ventral, dorsomedial, and dorsolateral striatum, while mice performed a perceptual and value-based decision task. Surprisingly, dopamine axon activity was similar across all three areas. At a glance, the activity multiplexed different variables such as stimulus-associated values, confidence, and reward feedback at different phases of the task. Our modeling demonstrates, however, that these modulations can be inclusively explained by moment-by-moment changes in the expected reward, that is the temporal difference error. A major difference between areas was the overall activity level of reward responses: reward responses in dorsolateral striatum were positively shifted, lacking inhibitory responses to negative prediction errors. The differences in dopamine signals put specific constraints on the properties of behaviors controlled by dopamine in these regions.


Neuron class-specific responses govern adaptive myelin remodeling in the neocortex

December 18, 2020

Myelin plasticity is critical for neurological function, including learning and memory. However, it is unknown whether this plasticity reflects uniform changes across all neuronal subtypes, or whether myelin dynamics vary between neuronal classes to enable fine-tuning of adaptive circuit responses. We performed in vivo two-photon imaging of myelin sheaths along single axons of excitatory callosal neurons and inhibitory parvalbumin-expressing interneurons in adult mouse visual cortex. We found that both neuron types show homeostatic myelin remodeling under normal vision. However, monocular deprivation results in adaptive myelin remodeling only in parvalbumin-expressing interneurons. An initial increase in elongation of myelin segments is followed by contraction of a separate cohort of segments. This data indicates that distinct classes of neurons individualize remodeling of their myelination profiles to diversify circuit tuning in response to sensory experience.


Sung Min Yang, Katrin Michel , Vahbiz Jokhi , Elly Nedivi , Paola Arlotta 

Continuous Whole-Body 3D Kinematic Recordings across the Rodent Behavioral Repertoire

December 16, 2020

In mammalian animal models, high-resolution kinematic tracking is restricted to brief sessions in constrained environments, limiting our ability to probe naturalistic behaviors and their neural underpinnings. To address this, we developed CAPTURE (Continuous Appendicular and Postural Tracking Using Retroreflector Embedding), a behavioral monitoring system that combines motion capture and deep learning to continuously track the 3D kinematics of a rat's head, trunk, and limbs for week-long timescales in freely behaving animals. CAPTURE realizes 10- to 100-fold gains in precision and robustness compared with existing convolutional network approaches to behavioral tracking. We demonstrate CAPTURE's ability to comprehensively profile the kinematics and sequential organization of natural rodent behavior, its variation across individuals, and its perturbation by drugs and disease, including identifying perseverative grooming states in a rat model of fragile X syndrome. CAPTURE significantly expands the range of behaviors and contexts that can be quantitatively investigated, opening the door to a new understanding of natural behavior and its neural basis.

Jesse D Marshall , Diego E Aldarondo , Timothy W Dunn , William L Wang , Gordon J Berman , Bence P Ölveczky 

Molecular classification of zebrafish retinal ganglion cells links genes to cell types to behavior

December 15, 2020

Retinal ganglion cells (RGCs) form an array of feature detectors, which convey visual information to central brain regions. Characterizing RGC diversity is required to understand the logic of the underlying functional segregation. Using single-cell transcriptomics, we systematically classified RGCs in adult and larval zebrafish, thereby identifying marker genes for >30 mature types and several developmental intermediates. We used this dataset to engineer transgenic driver lines, enabling specific experimental access to a subset of RGC types. Expression of one or few transcription factors often predicts dendrite morphologies and axonal projections to specific tectal layers and extratectal targets. In vivo calcium imaging revealed that molecularly defined RGCs exhibit specific functional tuning. Finally, chemogenetic ablation of eomesa+ RGCs, which comprise melanopsin-expressing types with projections to a small subset of central targets, selectively impaired phototaxis. Together, our study establishes a framework for systematically studying the functional architecture of the visual system.

Yvonne Kölsch , Joshua Hahn , Anna Sappington , Manuel Stemmer , António M Fernandes , Thomas O Helmbrecht , Shriya Lele , Salwan Butrus , Eva Laurell , Irene Arnold-Ammer , Karthik Shekhar , Joshua R Sanes , Herwig Baier