AGE DEPENDENT EFFECT OF SOCIAL ISOLATION ON ANXIETY, SOCIAL BEHAVIOR AND NEURAL SUBSTRATES IN ZEBRAFISH

Brain aging is characterized by cognitive decline related to progressive synaptic degradation. In zebrafish aging progression resembles human one, making these fish an intriguing model to explore the interplay among aging, behaviour, synaptic integrity and environmental stress. We combined in zebrafish deep learning based behavioral analysis with confocal microscopy based synaptic reconstruction, to correlate behavioral and synaptic changes at different ages, in particular those emerging in response to the social isolation stress paradigm.
Through DeepLabCut and MoSeq tools and custom python pipline, we observed that social deprivation significantly increased anxiety related behaviors in juvenile and adult fish compared to their controls, while this effect was not present in aged ones. Such behavioral modification was coupled with a significant increment in glutamatergic synapses, indicative for long term synaptic plasticity, in brain regions related to stress (the homologue of mammalian amygdala) as revealed by Golgi-Cox staining and immunostaining for excitatory synaptic markers.
When investigating social behavior, we found that the juvenile isolated fish were less social respect to their control, presenting conspecific avoidance and enhanced freezing behavior, an effect not detected in adult and aged individuals. Confirmatory factor analysis revealed that in juvenile fish modifications in social behavior were predicted by the anxiety.
Our findings indicate that social isolation has an age-dependent effect on animals’ behavior and related neural substrates, with younger animals exhibiting greater behavioral adaptability and neural plasticity respect to aged ones, which, in opposition, result in less responsive to environmental perturbations.