Venue: Centre Broca
Pr. Linda Simmler
Univ. Basel, Switzerland
Invited by Daria Ricci (Neurocentre Magendie)
Title
From head-twitching to synaptic plasticity: Pre-clinical research on psilocybin
Abstract
Psilocybin is a psychedelic compound which induces hallucination-like acute effects in humans. Upon ingestion, psilocybin is converted rapidly into its active metabolite psilocin, which is a partial agonist at the 5HT2A receptor and also potently binds the 5HT2C and 5HT1A receptors. Recently, psilocybin and related psychedelic compounds have gained much attention since clinical studies found that single doses can induced rapid and sustained antidepressant effects, even in patients with depression resistant to conventional treatment. The long-lasting nature of these clinical effects are through to be due to neuroplasticity. However, on a synaptic level, little is known about psychedelic-induced synaptic plasticity. Furthermore, a causal link to its antidepressant effect has yet to be established. My team and I use mice and state-of-the-art circuits neuroscience approaches to investigate psilocybin’s acute effects, long-term synaptic plasticity and long-lasting behavioral effects. In this seminar, I will present our findings on acute behavioral effects like head-twitching and its relationship to psilocin brain levels. I will further focus on our findings on long-lasting forms of synaptic plasticity induced after a single dose of psilocybin, which we assessed using whole-cell patch-clamp recordings of mouse brain slices. I will discuss how our findings may lead to identify the synaptic plasticity and neuronal circuits underlying psilocybin’s antidepressant effects, which would significantly increase the neurobiological understanding of a very promising treatment approach.
Key publications
Simmler LD, Li Y, Hadjas LC, Hiver A, van Zessen R, Lüscher C: Dual action of ketamine confines addiction liability. Nature, 2022, 608(7922): 368-373.
Li Y, Simmler LD, Van Zessen R, Flakowski J, Wan JX, Deng F, Li YL, Nautiyal KM, Pascoli V, Lüscher C: Synaptic mechanism underlying serotonin modulation of transition to cocaine addiction. Science 2021, 373(6560): 1252-1256.
Hadjas LC, Schartner MM, Cand J, Creed MC, Pascoli V, Lüscher C, Simmler LD: Projection-specific deficits in synaptic transmission in adult Sapap3-knockout mice. Neuropsychopharmacol 2020, 45(12): 2020-2029.
Hadjas LC, Lüscher C, Simmler LD: Aberrant habit formation in the Sapap3-knockout mouse model of obsessive-compulsive disorder. Sci Rep 2019, 9(1): 12061.
Simmler LD, Anacker AMJ, Levin MH, Vaswani NM, Gresch PJ, Nackenoff AG, Anastasio NC, Stutz SJ, Cunningham KA, Wang J, Zhang B, Henry LK, Stewart A, Veenstra-VanderWeele J, Blakely RD: Serotonin transporter blockade contributes to the behavioral, neuronal, and molecular effects of cocaine. Br J Pharmacol 2017, 174(16): 2716-2738.
Simmler LD, Buser TA, Donzelli M, Schramm Y, Dieu LH, Huwyler J, Chaboz S, Hoener MC, Liechti ME: Pharmacological characterization of designer cathinones in vitro. Br J Pharmacol 2013, 168(2): 458-470.
Meet the speaker!
You are a research staff ? Write to ">Julia Goncalves who will organize the schedule.
You are a PhD student? You can register to share some pizza after the talk. Registration opens 3 weeks before.
PhD seminars are organized by the NBA, Bordeaux Neurocampus, and the Bordeaux Neurocampus Graduate Program.
