High-resolution tracking of unconfined zebrafish behavior reveals stimulatory and anxiolytic effects of psilocybin.

Serotonergic psychedelics are emerging therapeutics for psychiatric disorders, yet their underlying mechanisms of action in the brain remain largely elusive. Here, we developed a wide-field behavioral tracking system for larval zebrafish and investigated the effects of psilocybin, a psychedelic serotonin receptor agonist. Machine learning analyses of precise body kinematics identified latent behavioral states reflecting spontaneous exploration, visually-driven rapid swimming, and irregular swim patterns following stress exposure. Using this method, we found that acute psilocybin treatment has two behavioral effects: [i] facilitation of spontaneous exploration ("stimulatory") and [ii] prevention of irregular swim patterns following stress exposure ("anxiolytic"). These effects differed from the effect of acute SSRI treatment and were rather similar to the effect of ketamine treatment. Neural activity imaging in the dorsal raphe nucleus suggested that psilocybin inhibits serotonergic neurons by activating local GABAergic neurons, consistent with psychedelic-induced suppression of serotonergic neurons in mammals. These findings pave the way for using larval zebrafish to elucidate neural mechanisms underlying the behavioral effects of serotonergic psychedelics.

Left anterior descending artery revascularization with the right internal thoracic artery T-graft: the 'reverse composite' configuration.

OBJECTIVES: The use of bilateral internal thoracic artery graft for myocardial revascularization has improved the long-term survival and decreased the rate of repeat interventions in patients. A key technical factor for complete arterial revascularization is sufficient length of the internal thoracic artery (ITA) graft. The purpose of this study was to compare early and long-term outcomes of 'standard composite' grafting and 'reverse composite' grafting. In the former, the left ITA (LITA) is connected to the left anterior descending artery, and the right ITA is connected end-to-side to the LITA for revascularization of the left circumflex artery. In 'reverse composite' grafting, the LITA is connected to the left circumflex artery, and the right ITA is connected end-to-side to the LITA, for revascularization of the left anterior descending artery. METHODS: We compared the outcomes of 1365 patients who underwent coronary artery bypass grafting in Tel-Aviv Sourasky Medical Centre, using bilateral ITA as standard composite versus 'reverse composite' grafts, between January 1996 and December 2011. A propensity score matching analysis compared 132 pairs of patients who underwent bilateral ITA by the 2 modes. RESULTS: Twelve hundred and thirty patients underwent standard 'composite' grafts and 135 underwent 'reverse composite' grafts. Early mortality and early adverse effects did not differ significantly between the groups. After matching, the difference in late mortality between the groups was not statistically significant. CONCLUSIONS: This study suggests that revascularization of the left anterior descending with the right ITA, arising from an in situ LITA, is safe and provides early outcomes and long-term survival that are not significantly different from those of the standard composite grafting technique. However, there was evidence of better survival in the standard composite group.