Assessing Social Engagement in Heterogeneous Groups of Zebrafish: A New Paradigm for Autism-Like Behavioral Responses

Abstract

Because of its highly developed social character, zebrafish is a promising model system for the study of the genetic and neurochemical basis of altered social engagement such as is common in autism and schizophrenia. The traditional shoaling paradigm investigates social cohesion in homogeneous groups of zebrafish. However, the social dynamics of mixed groups is gaining interest from a therapeutic point of view and thus warrants animal modeling. Furthermore, mutant zebrafish are not always available in large numbers. Therefore, we developed a new paradigm that allows exploring shoaling in heterogeneous groups. The effects of MK-801, a non-competitive antagonist of the glutamate N-methyl-D-aspartate (NMDA) receptor, on social cohesion were studied to evaluate the paradigm. The drug has previously been shown to mimic aspects of autism and schizophrenia. Our results show that a single MK-801-treated zebrafish reduced social cohesion of the entire shoal drastically. Preliminary observations suggest that the social dynamics of the shoal as a whole was altered.

Oxytocin Receptors Regulate Social Preference in Zebrafish

“…Shoaling in adult zebrafish. Shoaling data for shoals containing four fish was analysed for the following social parameters: average inter-fish distance (IFD) 25 , nearest neighbour distance (NND) 48 , and farthest neighbour distance (FND) 49 . Initial analyses revealed one vehicle-treated shoal as scoring more than two standard deviations above the mean for IFD and NND, and very close to two standard deviations above the mean for FND.…”

“…Similarly, levels of dopamine and serotonin are modulated in socially interacting fish [59][60][61] and social preference behaviour decreases after treatment with a dopamine D1 receptor antagonist 62 . Moreover, NMDA receptor antagonists inhibit social preference in both adult 44,49,63 and larval 27 zebrafish. In rodents, release of dopamine 64 , and serotonin 65 as well as excitation-inhibition balance 66 have been suggested as key mechanisms for the actions of OT on social behaviour.…”

Development of social behaviour in young zebrafish

“…Social learning in adult zebrafish is dependent upon N-methyl-D-Aspartate (NMDA) Receptor signalling(Maaswinkel et al, 2013) and we first assessed whether manipulating this pathway altered the social preference and interaction behaviour of zebrafish larvae. The NMDA receptor antagonist MK-801 was acutely administered at a concentration of 100 μM for 1 hour prior to assaying three week old zebrafish (Fig.…”

“…MK-801 treated larvae show strongly reduced bout periodicity and do not produce conventional forward swims, which could explain the observed deficit in coordinated behaviour. Such movement impairments will also affect the ability of treated fish to shoal, and might explain why adult zebrafish exposed to a lower concentration (5 μM) of MK- 801 exhibited disrupted shoal cohesion(Maaswinkel et al, 2013).…”

Zebrafish models for translational neuroscience research: from tank to bedside

“…The use of zebrafish to target social deficits is based on rich social behaviors in this species [7]. For example, zebrafish prefer to swim in shoals (Figure 4C), and the disruption of this group-forming behavior by various environmental, pharmacological, or genetic factors can be easily assessed [14,17,54]. Fully automated video tracking tools can ‘extract’ zebrafish social phenotypic data by monitoring several fish in parallel [48] and analyzing the proximity of three pairs of their body points relative to each other (see Figure 4D for details).…”