Modulation of the default mode network hub in the mouse brain by lysergic acid diethylamide: Insights from functional imaging

Aims. Psychedelics produce fast and persistent antidepressant effects and induce neuroplasticity resembling the effects of clinically approved antidepressants. We have recently found that lysergic acid diethylamide (LSD) directly bind to TrkB, the receptor for BDNF. Our data suggest that antidepressant and plasticity promoting-effect of psychedelics are mediated by TrkB. Our objective is to test in vivo the effect of LSD on brain functional connectivity, more specifically on the default mode network, and the impact of the modulation of TrkB receptor on this effect. Methods. Functional Ultrasound (fUS – Iconeus) allows the quantitative imaging of activation and of connectivity in the mouse brain. The typical experimental protocol consisted of resting-state acquisitions under medetomidine anesthesia (1 mg/kg) of 12 weeks old female mice. After a 10-min baseline imaging acquisition of 4 coronal planes, LSD (0.1 mg/kg) was administered intraperitoneally, followed by 2 imaging acquisition of 10 min each. Then, atipamezole was injected (1 mg/kg) to reverse the medetomidine effect. The temporal Pearson correlation coefficient r between each ROIs was computed and represented in a correlation matrix. Results. Preliminary data are showing an increase of functional connectivity between areas of the default mode network, including the thalamus, the retrosplenial area, the hippocampus and the medial forebrain bundle system, after LSD injection. Ongoing work involves the assessment of other TrKB ligands and their impact on this functional hub. Conclusions. We introduce fUS as a robust, specific and sensitive modality to monitor LSD effects on brain functional connectivity in the mouse brain.