Neuromodulatory Regulation of Behavioral Individuality in Zebrafish

Abstract

Summary Inter-individual behavioral variation is thought to increase fitness and aid adaptation to environmental change, but the underlying mechanisms are poorly understood. We find that variation between individuals in neuromodulatory input contributes to individuality in short-term habituation of the zebrafish (Danio Rerio) acoustic startle response (ASR). ASR habituation varies greatly between individuals, but differences are stable over days and are heritable. Acoustic stimuli that activate ASR-command Mauthner cells also activate dorsal raphe nucleus (DRN) serotonergic neurons, which project to the vicinity of the Mauthner cells and their inputs. DRN neuron activity decreases during habituation in proportion to habituation and a genetic manipulation that reduces serotonin content in DRN neurons increases habituation, whereas serotonergic agonism or DRN activation with ChR2 reduces habituation. Finally, level of rundown of DRN activity co-segregates with extent of behavioral habituation across generations. Thus, variation between individuals in neuromodulatory input contributes to individuality in a core adaptive behavior.

Histone H4 acetylation regulates behavioral inter-individual variability in zebrafish

“…In addition, genes located near the candidate regions are significantly related to transcriptional regulation, so differences in their expression might be amplified and this ultimately could lead to differences in processes like cognition or visual response, as our RNA-seq results suggested. Previous work has described how inter-individual variability in other behavioral paradigms underlies in different physiological processes like neurogenesis (Freund et al , 2013; Simola et al , 2015) and serotonin signaling (Kain et al , 2012; Pantoja et al , 2016). As some of the target genes of the YY1/HDAC1 pathway are related to neurogenesis, like neurog1 (Sun et al , 2001), it will be interesting to study if gene expression differences in these transcription factors could lead to alterations in neurogenesis and/or serotonin pathway.…”

“…We used zebrafish from 5 to 8 days post fertilization (dpf) to dissect the molecular substrates of behavioral inter-individual variability. Laboratory zebrafish larvae show individuality in behavior (Pantoja et al , 2016) and they present some advantages such as its wide genomic information, the simplicity of its pharmacological treatments and the possibility to do large-scale behavioral analysis. Additionally, it is relevant to use a species in which we can observe directly developmental changes, as some of the mechanisms responsible for behavioral individuality are likely accumulated during development (Fraga et al , 2005).…”

The structure of behavioral variation within a genotype

“…Substantial variation in specific behavioral measures, even in inbred lines raised in standardized conditions has been observed in several clonal animals, including: geckoes (of ethology, 2018), amazonian mollies (Bierbach et al, 2017), aphids and nematodes (Schuett et al, 2011;Stern et al, 2017). Genetic model systems hold particular promise for the mechanistic dissection of this variation, and intragenotypic variability (IGV) in behavior has been characterized in mice (Freund et al, 2013), zebrafish (Pantoja et al, 2016) and Drosophila. In flies, IGV of many behaviors has been studied, including: phototaxis (Kain et al, 2012), locomotor handedness and wing-folding , spontaneous microbehaviors (Kain et al, 2013;Todd et al, 2017), thermal preference and objectfixated locomotion (Liu et al, 2018).…”

Measuring Behavioral Individuality in the Acoustic Startle Behavior in Zebrafish

“…Automated analysis of behavioral movies is performed with MATLAB scripts. This protocol was adapted from two of our previously published papers (Levitz et al , 2013; Pantoja et al , 2016). The zBox provides an easy to setup flexible platform for behavioral experiments in zebrafish larvae.…”

“…The work and experimental approach described here have been adapted from previous research published in Nature Neuroscience (Levitz et al , 2013) and Neuron (Pantoja et al , 2016). Further information about uses for the zBox are reported in a study that investigated the role of neuropeptides in the partition of arousal behaviors in zebrafish (Woods et al , 2014).…”