Jonathan Fischell

TL;DR: It is shown that the metabolism of (R,S)-ketamine to (2S,6S;2R,6R)-hydroxynorketamine (HNK) is essential for its antidepressant effects, and that the HNK enantiomer exerts behavioural, electroencephalographic, electrophysiological and cellular antidepressant-related actions in mice.

TL;DR: It is suggested that the ability of L-655,708 to restore excitatory synaptic strength rapidly may underlie its ability to restore stress-induced behavioral alterations rapidly, supporting evidence that dysfunction of multipleexcitatory synapses in cortico-mesolimbic reward pathways contributes, in part, to the genesis of depression.

TL;DR: It is found that (2R,6R)-HNK enhances excitatory synaptic transmission in the hippocampus through a concentration-dependent, NMDAR-independent, and synapse-selective increase in glutamate release probability with no direct actions on AMPAR function.

TL;DR: Plaque burden, as estimated by VWV, can be measured reliably with a 3D US technique using a clinical scanner, as well as 2D and 3D measures of plaque morphometry that can be applied in a clinical environment.

TL;DR: It is demonstrated that (2R,6R)-HNK inhibits synaptic NMDARs and subsequently elicits the same signal transduction pathway previously associated with N MDAR inhibition by ketamine, and that the effects of ( 2R, 6R)- HNK on intracellular signalling are coupled to NMD AR inhibition.