RT Journal Article SR Electronic T1 Functional and ultrastructural analysis of reafferent mechanosensation in larval zebrafish JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.05.04.442674 DO 10.1101/2021.05.04.442674 A1 Iris Odstrcil A1 Mariela D. Petkova A1 Martin Haesemeyer A1 Jonathan Boulanger-Weill A1 Maxim Nikitchenko A1 James A. Gagnon A1 Pablo Oteiza A1 Richard Schalek A1 Adi Peleg A1 Ruben Portugues A1 Jeff Lichtman A1 Florian Engert YR 2021 UL http://biorxiv.org/content/early/2021/05/06/2021.05.04.442674.abstract AB All animals need to differentiate between exafferent stimuli, which are caused by the environment, and reafferent stimuli, which are caused by their own movement. In the case of mechanosensation in aquatic animals, the exafferent inputs are water vibrations in the animal’s proximity, which need to be distinguished from the reafferent inputs arising from fluid drag due to locomotion. Both of these inputs are detected by the lateral line, a collection of mechanosensory organs distributed along the surface of the body.In this study, we characterize in detail how the hair cells, which are the receptor cells of the lateral line, discriminate between such reafferent and exafferent signals in zebrafish larvae. Using dye labeling of the lateral line nerve, we visualize two parallel descending inputs that can influence lateral line sensitivity. We combine functional imaging with ultra-structural EM circuit reconstruction to show that cholinergic signals originating from the hindbrain transmit efference copies that cancel out self-generated reafferent stimulation during locomotion, and that dopaminergic signals from the hypothalamus may have a role in threshold modulation both in response to locomotion and salient stimuli. We further gain direct mechanistic insight into the core components of this circuit by loss-of-function perturbations using targeted ablations and gene knockouts.We propose that this simple circuit is the core implementation of mechanosensory reafferent suppression in these young animals and that it might form the first instantiation of state-dependent modulation found at later stages in development.Competing Interest StatementThe authors have declared no competing interest.