Zebrafish oxytocin neurons drive nocifensive behavior via brainstem premotor targets

Abstract

Animals have evolved specialized neural circuits to defend themselves from pain-and injurycausing stimuli. Using a combination of optical, behavioral and genetic approaches in the larval zebrafish, we describe a novel role for hypothalamic oxytocin (OXT) neurons in the processing of noxious stimuli. In vivo imaging reveals that a large and distributed fraction of zebrafish OXT Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

A Bidirectional Network for Appetite Control in Larval Zebrafish

“…Thus, during food-deprivation, the cH may play complementary roles such as the sensitization of the LH and/or other feeding-related circuits (as discussed above), or drive alternative behavioral programs, like foraging or energy-conserving measures (see Supplementary File 1 - Conceptual Circuit Model for a more in-depth discussion). Given that cH neurons appear also to be activated by aversive stimuli (Randlett et al, 2015; Wee et al, 2019), they might quite generally encode a negative valence state, of which being hungry in the absence of food is an example. This then suggests that the silence of these neurons in a hungry fish where food is present implies a positive valence state, a notion that is in ready agreement with human subjective experience.…”

Social isolation modulates appetite and defensive behavior via a common oxytocinergic circuit in larval zebrafish

“…1a-b, Supplementary Movie 1, Supplementary Data 1). Many of these same regions are activated by noxious or aversive stimuli 6,7 ; they may thus represent the signature activity pattern of a negative internal state, which can be similarly triggered by social deprivation. Neurons expressing the peptide oxytocin (OXT) are abundant in the PO and PT 6,12,13 regions, and as we describe below, OXT-positive neuron clusters in both of these areas (OXT PO and OXT PT respectively) display greater activity in socially-isolated fish.…”

“…Many of these same regions are activated by noxious or aversive stimuli 6,7 ; they may thus represent the signature activity pattern of a negative internal state, which can be similarly triggered by social deprivation. Neurons expressing the peptide oxytocin (OXT) are abundant in the PO and PT 6,12,13 regions, and as we describe below, OXT-positive neuron clusters in both of these areas (OXT PO and OXT PT respectively) display greater activity in socially-isolated fish. To acquire a more precise quantitation of OXT activity in relation to the social environment, we measured pERK activity for individual GFP-labeled OXT neurons ( Tg(oxt:GFP) ), as well as surrounding non-OXT PO and PT neurons, in high resolution confocal microscopic images of dissected brains 6 (Fig.…”

“…OXT has also been described as a potent regulator of appetite 4,5 . We reported recently that the larval zebrafish OXT circuit encodes a response to aversive, particularly noxious stimuli and directly drives nocifensive behavior via brainstem premotor targets 6 . Moreover, studies in both zebrafish 6–8 and mammals 9,10 suggest that the OXT-expressing neuronal population is anatomically and functionally diverse, and might also modulate multiple behaviors in zebrafish.…”

“…We reported recently that the larval zebrafish OXT circuit encodes a response to aversive, particularly noxious stimuli and directly drives nocifensive behavior via brainstem premotor targets 6 . Moreover, studies in both zebrafish 6–8 and mammals 9,10 suggest that the OXT-expressing neuronal population is anatomically and functionally diverse, and might also modulate multiple behaviors in zebrafish. Here, in a brain-wide screen 11 for neuronal populations whose activity reflects social context, we show that larval zebrafish oxytocinergic circuits display diverse responses to conspecific chemosensory stimuli, and are key effectors for social context modulation of nociceptive and appetite-driven behaviors.…”