What an amazing world we live in that this information is available for free in an easy to digest manner. Thank you so much for the effort, very informative!
I'm thinking i might fast skip through your videos and like and share them all. They are so important for people to hear and understand. You make understanding so much easier.
I am in finance and joining a psychedelic company specifically targeting the 5ht2a receptor and I was looking for videos to help me understand what we are offering our patients. This is very good! I'll have to watch a few times as I'm more visual than I am a verbal learner! but the best video I've seen so far.
Excellent lesson . You managed to concisely present a wide range of topics and details in an " easy " to understand manner for the layperson - like me . Thank you .
Fantastic presentation. Really enjoying percolating in your teachings. Im a retired nurse and feel that the potential for these drugs in managing addictions, PTSD, depression, and end of life anxiety is going to be an absolute game-changer in the medical field. Not to mention its entheogenic potentials for the rest of us! All the best with your studies and I hope you continue to find time to share your knowledge with us.
You’re so good at explaining things! I had no idea about the spillover effect before, definitely something to I want to look into further. Thanks for the awesome content.
Outstanding video. You’re very, very good at explaining neuroscience clearly. (I say that as a university prof who spends time thinking about how to explain things clearly to my students.)
There's something I can't really wrap my head around. We know that 5-HT2A receptor activation in the deep cortical layers trigger glutamate release (and NMDA/AMPA activation) in layer V, thus making layer V pyramidal neurons (DMN) "more likely to fire." (These events are shown to be regulated by mGlu2, which are located at the cortical presynaptic terminals and work as inhibitory autoreceptors for glutamate; mGlu2 agonists attenuate the effects of psychedelics and antagonists increase them.) I remember you saying elsewhere that the DMN basically "controls" various high-level brain regions such as hippocampus and when the activity of the DMN decreases, the structures it controls become more independent. The "DMN activity decrease -> more independent brain regions" part makes sense, but I coudn't really understand the connection between 5HT2A agonism and activity decrease. How is it that 5HT2AR agonists decrease the activity in the DMN while also making its neurons more likely to fire? I'm not very well-versed in the imaging techniques such as BOLD fMRI but is it safe to say that by "activity decrease" you mean the summation of the desynchronized signals decrease while individual signals increase? Like constructive and destructive interference in physics? Or are we dealing with inhibitory interneurons here?
Great question. The short answer is we don't know exactly why the DMN becomes deactivated as a result of high (excitatory) 5-HT2A agonism at exactly those regions. My hunch is that it's related to desynchronization, in the way that you suggested (if I understood you correctly). I.e., the neurons within DMN regions are on the whole more active, but they're activating asynchronously such that when you average over hundreds of thousands of them you at a given point in time then you get a net decrease relative to placebo/baseline. This is why, ultimately, functional connectivity between regions (i.e., correlations between regional activity over time) is a bit more informative - it tells you, independent of absolute activation, how much regions are likely to be interacting with each other in a coordinated fashion. Also I should mention that fMRI cannot disentangle excitatory and inhibitory neurons. Any neuron that activates leads to more or less similar oxygen changes (i.e. BOLD signal). Inhibitory interneurons will not show up as negative signal.
Hi! ! ! ! Thanks for your Channel! ! ! What if the stimulant response associated with glutamate predominates in a disorderly, erratic and disseminated way when using psychedelics? How is that response controlled? Thanks! ! ! Paula Bustamante.
If a psychedelic binds to a 5-HT2A receptor and causes more glutmate to fire and more AMPA receptors to be recruited, is that then what they call Long term potentiation (LTP)?
Dear Manesh. Thank your for your scientific contribution. I have a technical question to ask: According to what you explained, since the most activated receptor by psychedelic is the 5-HT2a, the result is the increase of excitatory neurotransmitter glutamate release (predominant to Gaba). Consequently the net effect is the increase of neurons activation in the brain. In this regard, I wonder whether the iperattivation of Ampa receptors and the amplification of glutamate signals, could represent an hazard for people suffering from psychiatric and neurological diseases related to an iperattivation of glutamatergic neurotransmission. Thank you.
Hi Davide. This is a really good question. I assume you are primarily referring to the possibility of inducing seizures via over excitation of glutamatergic transmission. Interestingly, psychedelics are not known to induce seizures. This is very likely due to two things: (1) the simultaneous effects on GABA attenuates and manages this increased activity and prevents it from spreading uncontrollably and (2) the classic psychedelics all also strongly affect 5-HT1A receptors, which have an inhibitory effect on neuron activity and which counter the effects of 5-HT2A agonism. So there appear to be checks and balances in place which prevent psychedelics from inducing too much glutamatergic stimulation.
hi = I cant find part 2 of this video, its really important for me to get this now you have my full interest and my full attention! that aside, you are a talentented dude. Very useful to me, and for my job. thanks.
@@ThePsychedelicScientist many thanks I believed. And assumed I couldn't find it. How wrong my beliefs were?!! Thanks, I feel like Tom hanks personally replied to ME!
