Summary Simultaneous recordings of large populations of neurons in behaving animals allow detailed observation of high-dimensional, complex brain activity. However, experimental approaches often focus on singular behavioral paradigms or brain areas. Here, we recorded whole-brain neuronal activity of larval zebrafish presented with a battery of visual stimuli while recording fictive motor output. We identified neurons tuned to each stimulus type and motor output, and discovered groups of neurons in the anterior hindbrain that respond to different stimuli that elicit similar behavioral responses. These convergent sensorimotor representations were only weakly correlated to instantaneous motor activity, suggesting that they critically inform, but do not directly generate, behavioral choices. To catalog brain-wide activity beyond explicit sensorimotor processing, we developed an unsupervised clustering technique that organizes neurons into functional groups. These analyses enabled a broad overview of the functional organization of the brain, and revealed numerous brain nuclei whose neurons exhibit concerted activity patterns.

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:

Medial and lateral hypothalamic loci are known to suppress and enhance appetite, respectively, but the dynamics and functional significance of their interaction have yet to be explored. Here we report that, in larval zebrafish, primarily serotonergic neurons of the ventromedial caudal hypothalamus (cH) become increasingly active during food deprivation, whereas activity in the lateral hypothalamus (LH) is reduced. Exposure to food sensory and consummatory cues reverses the activity patterns of these two nuclei, consistent with their representation of opposing internal hunger states. Baseline activity is restored as food-deprived animals return to satiety via voracious feeding. The antagonistic relationship and functional importance of cH and LH activity patterns were confirmed by targeted stimulation and ablation of cH neurons. Collectively, the data allow us to propose a model in which these hypothalamic nuclei regulate different phases of hunger and satiety and coordinate energy balance via antagonistic control of distinct behavioral outputs.

24How brains encode social stimuli and transform these representations into advantageous 25 behavioral responses is not well-understood. Here, we show that social isolation activates an 26 oxytocinergic, nociceptive circuit in the larval zebrafish hypothalamus. We further demonstrate 27 that chemical cues released from conspecific animals modulate its activity to regulate defensive 28 behaviors and appetite. Our collective data reveals a model through which social stimuli can be 29 integrated into fundamental neural circuits to mediate adaptive behaviour. 30 31 32 33 34In mammals, signaling in oxytocinergic (OXT) circuits modulates a wide spectrum of socially 36 driven behaviors, ranging from pair bonding and parental care to the responses to stress and 37 pain 1-3 . OXT has also been described as a potent regulator of appetite 4,5 . We reported recently 38 that the larval zebrafish OXT circuit encodes a response to aversive, particularly noxious stimuli 39 and directly drives nocifensive behavior via brainstem premotor targets 6 . Moreover, studies in 40 both zebrafish 6-8 and mammals 9,10 suggest that the OXT-expressing neuronal population is 41 anatomically and functionally diverse, and might also modulate multiple behaviors in zebrafish. 42Here, in a brain-wide screen 11 for neuronal populations whose activity reflects social context, we 43show that larval zebrafish oxytocinergic circuits display diverse responses to conspecific 44 chemosensory stimuli, and are key effectors for social context modulation of nociceptive and 45 appetite-driven behaviors. Our results reveal a simple algorithm by which neuromodulatory 46 neurons can represent social context to exert flexible control over hard-wired behavioral drives. 47 48 RESULTS 49Brain-wide activity mapping of social isolation and its rescue by conspecific chemical cues 50Using pERK based whole-brain activity mapping (MAP-Mapping 11 ), neural activity in brains of 51 briefly (2 hrs) socially-isolated larvae (7 -8 days-post-fertilization; dpf) was compared to 52 animals that had been maintained in the presence of similarly-aged conspecifics. We found that 53 isolated fish showed an enhancement of neural activity in specific regions, including the 54 telencephalon (especially subpallium), hindbrain, locus coeruleus, area postrema, caudal 55 hypothalamus, preoptic area (PO, homolog of the hypothalamic paraventricular nucleus in 56 mammals) and posterior tuberculum (PT) ( Fig. 1a-b , Supplementary Movie 1, Supplementary 57Data 1). Many of these same regions are activated by noxious or aversive stimuli 6,7 ; they may 58 thus represent the signature activity pattern of a negative internal state, which can be similarly 59 triggered by social deprivation. Neurons expressing the peptide oxytocin (OXT) are abundant in 60 the PO and PT 6,12,13 regions, and as we describe below, OXT-positive neuron clusters in both of 61 these areas (OXT PO and OXT PT respectively) display greater activity in socially-isolated fish. To 62 acquire a more precise quantitation of OXT activi...