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Virtual reality · Behavior · Neuromodulation

Futility-induced passivity

A controlled transition from persistent swimming to passivity.

We combine a tail-free virtual-reality assay with whole-brain calcium imaging, quantitative behavior, and causal perturbations to understand the mechanisms underlying the transition.

© Marc Duque Ramírez
A freely swimming zebrafish alternates between swimming against the flow and giving up01

What we did

How the assay works.

A head-fixed, tail-free larval zebrafish swims against forward-moving gratings. During closed loop, each swim changes the visual feedback and signals effective forward motion. During open loop, swimming no longer affects the gratings and is therefore futile. Fish initially increase swimming vigor and struggle, then transiently stop swimming and become passive.

By using whole-brain imaging, we record calcium dynamics in both neurons and glia throughout this behavioral transition. Optogenetic, pharmacological, and genetic perturbations then test the contribution of specific cells and pathways.

© Marc Duque Ramírez
The tail-free virtual-reality assay switches from movement-dependent feedback to open loop01.1

Current directions

Dorsal raphe and circuit architecture

Current work tests how the serotonergic dorsal raphe and its downstream circuits may compute futility and modulate the transition to passivity. We combine connectomics from a whole-brain electron-microscopy dataset with whole-brain imaging, pharmacology, and optogenetic perturbations to investigate how this dorsal raphe population communicates with the norepinephrine–astroglia circuit described by Mu et al. (2019) and the habenula–raphe circuit described by Andalman et al. (2019), and whether these pathways are connected.

Methods

Futility-induced passivity using virtual realityWhole-brain imagingQuantitative behaviorConnectomics from whole-brain electron microscopyOptogenetic perturbationPharmacological perturbation

Next project

Pharmacology & plasticity