Forebrain Control of Behaviorally Driven Social Orienting in Zebrafish

Abstract

Deficits in social engagement are diagnostic of multiple neurodevelopmental disorders, including autism and schizophrenia [1]. Genetically tractable animal models like zebrafish (Danio rerio) could provide valuable insight into developmental factors underlying these social impairments, but this approach is predicated on the ability to accurately and reliably quantify subtle behavioral changes. Similarly, characterizing local molecular and morphological phenotypes requires knowledge of the neuroanatomical correlates of social behavior. We leveraged behavioral and genetic tools in zebrafish to both refine our understanding of social behavior and identify brain regions important for driving it. We characterized visual social interactions between pairs of adult zebrafish and discovered that they perform a stereotyped orienting behavior that reflects social attention [2]. Furthermore, in pairs of fish, the orienting behavior of one individual is the primary factor driving the same behavior in the other individual. We used manual and genetic lesions to investigate the forebrain contribution to this behavior and identified a population of neurons in the ventral telencephalon whose ablation suppresses social interactions, while sparing other locomotor and visual behaviors. These neurons are cholinergic and express the gene encoding the transcription factor Lhx8a, which is required for development of cholinergic neurons in the mouse forebrain [3]. The neuronal population identified in zebrafish lies in a region homologous to mammalian forebrain regions implicated in social behavior such as the lateral septum [4]. Our data suggest that an evolutionarily conserved population of neurons controls social orienting in zebrafish.

Late onset of Syt2a expression at synapses relevant to social behavior

“…Consistent with the above observations, we noticed an increase in Syt2a puncta in a region adjacent to the AC (aAC, Fig.3B, orange box), a region populated by neurons which are necessary for social behavior in the adult (Stednitz et al, 2018) and at 14 dpf (AT and PW, unpublished observation). We compared Syt2a puncta at 12 and 14 dpf, a time period in which social behavior becomes more robust, and found a 20% increase in Syt2 labeling in this aAC region ( Fig.3D).…”

“…Both inter-fish related social attraction and orienting as well as the detection of biological motion become established around 14 dpf (Dreosti et al, 2015;Larsch and Baier, 2018). We previously identified a genetically-defined population of lhx8a-positive neurons in the ventral forebrain of zebrafish larvae that is important for social behavior at 14 dpf (AT, PW, unpublished), as defined by ablation experiments similar to those in adult zebrafish (Stednitz et al, 2018). These cells are cholinergic (Stednitz et al, 2018), similarly to a population of cells in the basal forebrain in mammals (Zhao et al, 2003).…”

“…We investigated the expression profile of Syt2 during various stages of zebrafish larval development and, in particular, with a focus on synaptic protein changes that occur at critical time periods, for instance, during the establishment of complex behaviors. We recently demonstrated a requirement for the ventral telencephalon for social behavior (Stednitz et al, 2018), and a number of studies indicate that this behavior initiates around the second week of life (Dreosti et al, 2015;Larsch and Baier, 2018). These observations raise the question of whether synaptic connections of the putative social circuit already exist prior to 14 days postfertilization (dpf), and if they do, what changed to allow the behavior to become functional.…”

Evolutionary “Experiments” in Symbiosis: The Study of Model Animals Provides Insights into the Mechanisms Underlying the Diversity of Host–Microbe Interactions

“…[63] The optical transparency allows visualization of microbial and host cell dynamics in real time during critical process such as intestinal colonization. Because zebrafish are social animals with readily assayed social behaviors, [67] they provide an attractive model for studying the reciprocal impacts of resident microbes on social behaviors and the impacts of social interactions on microbiome structures. [65] The animal's small size and large populations also enable explorations of microbiome dynamics at the level of host populations.…”

“…[66] Such cohousing manipulations can also be used to explore the impact of microbes on social behaviors. Because zebrafish are social animals with readily assayed social behaviors, [67] they provide an attractive model for studying the reciprocal impacts of resident microbes on social behaviors and the impacts of social interactions on microbiome structures.…”