Bryan Roth

Psychedelics Activate 5-HT2A Neurons in Prefrontal Cortex In a groundbreaking study poised to reshape our understanding of psychedelic pharmacology and its neural substrates, a team of scientists has elucidated the precise cellular mechanisms by which

Psychedelics Activate 5-HT2A Neurons in Prefrontal Cortex
#psychedelics
scienmag.com/psychedelics...

Scientist on front lines of overdose crisis receives MacArthur 'genius' award Nabarun Dasgupta was recognized with a MacArthur "genius" award for work studying the deadly overdose crisis. He's also a front-line organizer, helping people survive.

My friend and colleague @nabarund.bsky.social !!!! www.npr.org/2025/10/08/n...

Winning a Nobel Prize Interrupted His Off-the-Grid Vacation Fred Ramsdell found out about his Nobel Prize nearly 12 hours after it was announced because he was on vacation in the Rockies.

Fred Ramsdell was parked at a campground in Montana on Monday when his wife suddenly started shouting. He first thought that maybe she had seen a grizzly bear. Instead, she had regained cell service and had seen a flood of text messages with the same news. “You just won the Nobel Prize!” she yelled.

Basically we confirmed the very first step in psychedelic drug action is to enhance excitability of those neurons. This, per my hypothesis, is the very first step in psychedelic drug action

The title is the entire paper.

Psychedelic compounds directly excite 5-HT2A layer V medial prefrontal cortex neurons through 5-HT2A Gq activation - Translational Psychiatry Translational Psychiatry - Psychedelic compounds directly excite 5-HT2A layer V medial prefrontal cortex neurons through 5-HT2A Gq activation

www.nature.com/articles/s41...
Finally out!!

Psychedelic compounds directly excite 5-HT2A layer V medial prefrontal cortex neurons through 5-HT2A Gq activation - Translational Psychiatry Translational Psychiatry - Psychedelic compounds directly excite 5-HT2A layer V medial prefrontal cortex neurons through 5-HT2A Gq activation

www.nature.com/articles/s41...
Finally out!!

For those who are still searching

Not at all--it's just amusing to me that one way to look at his trajectory is: "I came to Scripps to train with the giants of science. Sadly they did not offer me a position. Happily, years later, I won the Nobel Prize. Will they offer me a tenure-track position now?"

Kinda was at Scripps "Former Scripps Research assistant professor" AKA non-tenure-track/super-post-doctoral fellow
www.scripps.edu/news-and-eve...

Biased signaling via serotonin 5-HT2A receptor: From structural aspects to in vitro and in vivo pharmacology - PubMed G protein-coupled receptors (GPCRs) represent key drug targets, with approximately 30%-40% of all medications acting on these receptors. Recent advancements have uncovered the complexity of GPCR signa...

Nice review on biased signaling and #psychedelics
pubmed.ncbi.nlm.nih.gov/41049744/

The aggressive colorectal cancer subtype marker HTR2B has a dual role depending on the tumor microenvironment - PubMed Colorectal cancer (CRC) is the second-third most frequent cancer type in the Western countries, with significant inter- and intra-patient cellular heterogeneity. The transcriptomics-based CRC classifi...

5-HT2B and cancer?
pubmed.ncbi.nlm.nih.gov/41034989/

Biased signaling via serotonin 5-HT2A receptor: From structural aspects to in vitro and in vivo pharmacology - PubMed G protein-coupled receptors (GPCRs) represent key drug targets, with approximately 30%-40% of all medications acting on these receptors. Recent advancements have uncovered the complexity of GPCR signa...

Nice review on biased signaling and #psychedelics
pubmed.ncbi.nlm.nih.gov/41049744/

Cortical 5-HT2A receptors in depression and suicide: a systematic review and meta-analysis of in vivo and post-mortem imaging studies - Molecular Psychiatry Molecular Psychiatry - Cortical 5-HT2A receptors in depression and suicide: a systematic review and meta-analysis of in vivo and post-mortem imaging studies

5-HT2A receptors down in depression: Meta analysis
#psychedelics
www.nature.com/articles/s41...

My unvarnished thoughts on todays Nobel Prize and prizes and 'high impact journals'
open.substack.com/pub/zendudes...

I can’t speak about literature but they typically get the science prizes right. Certainly they did here.

It is informative that two of the
@NobelPrize
laureates: Brunkow and Ramsdell have not been elected to the
@theNASciences
nor have they been recognized by Lasker, Gairdner and so on....

Astrocytic Activation Completely Corrects Memory Performancein an Alzheimer's Disease Model https://www.biorxiv.org/content/10.1101/2025.09.29.679133v1

Wow!!

Dysfunction of cortical GABAergic projection neurons as a major hallmark in a model of neuropsychiatric syndrome Using advanced transcriptomic and physiological profiling, the authors identified deep-layer long-range GABAergic projection neurons as the most disrupted neuronal subtype and key contributor to brain...

Dysfunction of cortical GABAergic projection neurons as a major hallmark in a model of neuropsychiatric syndrome: Neuron www.cell.com/neuron/fullt...

So glad to hear I’m potentially qualified to be an Assistant Professor!

Submedius Thalamus Modulates Orbitofrontal Cortex Representations During Maternal Behavior in Mice https://www.biorxiv.org/content/10.1101/2025.09.18.677207v1

It's #FluorescenceFriday! Another movie from our preprint, showing exocytosis of VAMP2-pHluorin (live-cell TIRF, blue) correlated with 2-color STORM of spectrins (green) and clathrin-coated pits (magenta).
www.biorxiv.org/content/10.1...

Grin2b-mutant mice exhibit heightened remote fear via suppressed extinction and chronic amygdalar synaptic and neuronal dysfunction Amygdalar dysfunctions trigger suppressed fear extinction and enhanced remote fear responses in a Grin2b-mutant ASD mouse model.

Grin2b-mutant mice exhibit heightened remote fear via suppressed extinction and chronic amygdalar synaptic and neuronal dysfunction | Science Advances www.science.org/doi/10.1126/...

Grin2b-mutant mice exhibit heightened remote fear via suppressed extinction and chronic amygdalar synaptic and neuronal dysfunction Amygdalar dysfunctions trigger suppressed fear extinction and enhanced remote fear responses in a Grin2b-mutant ASD mouse model.

Grin2b-mutant mice exhibit heightened remote fear via suppressed extinction and chronic amygdalar synaptic and neuronal dysfunction | Science Advances www.science.org/doi/10.1126/...

Now this is useful!
PRESTO-TANGO selectivity data on chemical probes freely available!
Please RT
#gpcr
www.opnme.com/news/pdsp-ne...

Identification of a neural basis for energy expenditure in the mouse arcuate hypothalamus Wang et al. demonstrate that hypothalamic GABAergic Crabp1 neurons promote energy expenditure by targeting multiple nuclei in mice. These neurons are activated by cold and exercise but suppressed by l...

Identification of a neural basis for energy expenditure in the mouse arcuate hypothalamus: Neuron www.cell.com/neuron/fullt...

Impermanence and science "Sometimes you get the bear, and sometimes the bear gets you."

My thoughts on grant writing hell
open.substack.com/pub/zendudes...

Candace Pert - Wikipedia

Yes that is new and truly exciting. Just bummed that an old (and deceased) friend Candace Pert doesn't receive at least a mention as these findings would really resonate with her.
en.wikipedia.org/wiki/Candace...