Serotonergic Psychedelics Rapidly Modulate Evoked Glutamate Release in Cultured Cortical Neurons

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F25%3A43921492" target="_blank" >RIV/00023752:_____/25:43921492 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11120/25:43928181

Result on the web

<a href="https://doi.org/10.1111/jnc.70020" target="_blank" >https://doi.org/10.1111/jnc.70020</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/jnc.70020" target="_blank" >10.1111/jnc.70020</a>

Result language

angličtina

Original language name

Serotonergic Psychedelics Rapidly Modulate Evoked Glutamate Release in Cultured Cortical Neurons

Original language description

The serotonergic psychedelics psilocybin, LSD and DMT hold great promise for the development of new treatments for psychiatric conditions such as major depressive disorder, addiction and end-of-life anxiety. Previous studies in both animals and humans have confirmed the effects of these drugs on neuronal activity and plasticity. However, the understanding of the mechanisms of action of these substances is limited. Here we show rapid effects of psychedelics on presynaptic properties, using live cell imaging at the level of single synapses in primary rat cortical neurons. Using the genetically encoded reporter of synaptic vesicle fusion synaptopHluorin, we detected a reduced fraction of synaptic vesicles that fused in response to mild or strong electrical stimulation 3-30 min after application of serotonergic psychedelics. These effects were transient and no longer present 24 h after treatment. While DMT only reduced the total recycling pool, LSD and psilocin also reduced the size of the readily releasable vesicle pool. Imaging with the sensors for glutamate, iGluSnFR, and presynaptic calcium, synGCaMP6, showed that while psilocin and DMT increased evoked glutamate release, LSD and psilocin reduced evoked presynaptic calcium levels. Interestingly, psilocin also affected short-term plasticity leading to a depression of responses to paired stimuli. The rapid and drug-specific modulation of glutamatergic neurotransmission described in this study may contribute to distinct anxiolytic and antidepressant properties of serotonergic psychedelics.image

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30103 - Neurosciences (including psychophysiology)

Project

<a href="/en/project/GA20-25349S" target="_blank" >GA20-25349S: Psychoplastogenicity of psilocybin – the interplay of serotonergic mechanisms, sleep–wake cycle and neuroplasticity on memory consolidation</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Neurochemistry

ISSN

0022-3042

e-ISSN

1471-4159

Volume of the periodical

169

Issue of the periodical within the volume

3

Country of publishing house

GB - UNITED KINGDOM

Number of pages

19

Pages from-to

"e70020"

UT code for WoS article

001442307600001

EID of the result in the Scopus database

2-s2.0-85219607689