Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Presynaptic nanoscale components of retrograde synaptic signaling

Barti, Benjámin ; Dudok, Barna ; Kenesei, Kata ; Zöldi, Miklós ; Miczán, Vivien ; Balla, Gyula Y. ; Zala, Diana ; Tasso, Mariana ; Sagheddu, Claudia and Kisfali, Máté , et al. (2024) In Science Advances 10(22).
Abstract

While our understanding of the nanoscale architecture of anterograde synaptic transmission is rapidly expanding, the qualitative and quantitative molecular principles underlying distinct mechanisms of retrograde synaptic communication remain elusive. We show that a particular form of tonic cannabinoid signaling is essential for setting target cell–dependent synaptic variability. It does not require the activity of the two major endocannabinoid-producing enzymes. Instead, by developing a workflow for physiological, anatomical, and molecular measurements at the same unitary synapse, we demonstrate that the nanoscale stoichiometric ratio of type 1 cannabinoid receptors (CB1Rs) to the release machinery is sufficient to predict... (More)

While our understanding of the nanoscale architecture of anterograde synaptic transmission is rapidly expanding, the qualitative and quantitative molecular principles underlying distinct mechanisms of retrograde synaptic communication remain elusive. We show that a particular form of tonic cannabinoid signaling is essential for setting target cell–dependent synaptic variability. It does not require the activity of the two major endocannabinoid-producing enzymes. Instead, by developing a workflow for physiological, anatomical, and molecular measurements at the same unitary synapse, we demonstrate that the nanoscale stoichiometric ratio of type 1 cannabinoid receptors (CB1Rs) to the release machinery is sufficient to predict synapse-specific release probability. Accordingly, selective decrease of extrasynaptic CB1Rs does not affect synaptic transmission, whereas in vivo exposure to the phytocannabinoid Δ9-tetrahydrocannabinol disrupts the intrasynaptic nanoscale stoichiometry and reduces synaptic variability. These findings imply that synapses leverage the nanoscale stoichiometry of presynaptic receptor coupling to the release machinery to establish synaptic strength in a target cell–dependent manner.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Science Advances
volume
10
issue
22
article number
eado0077
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • pmid:38809980
  • scopus:85194871190
ISSN
2375-2548
DOI
10.1126/sciadv.ado0077
language
English
LU publication?
yes
id
7af5a4e5-5459-4583-ba16-60219e2c17f4
date added to LUP
2024-08-26 08:42:00
date last changed
2025-07-01 13:29:17
@article{7af5a4e5-5459-4583-ba16-60219e2c17f4,
  abstract     = {{<p>While our understanding of the nanoscale architecture of anterograde synaptic transmission is rapidly expanding, the qualitative and quantitative molecular principles underlying distinct mechanisms of retrograde synaptic communication remain elusive. We show that a particular form of tonic cannabinoid signaling is essential for setting target cell–dependent synaptic variability. It does not require the activity of the two major endocannabinoid-producing enzymes. Instead, by developing a workflow for physiological, anatomical, and molecular measurements at the same unitary synapse, we demonstrate that the nanoscale stoichiometric ratio of type 1 cannabinoid receptors (CB<sub>1</sub>Rs) to the release machinery is sufficient to predict synapse-specific release probability. Accordingly, selective decrease of extrasynaptic CB<sub>1</sub>Rs does not affect synaptic transmission, whereas in vivo exposure to the phytocannabinoid Δ<sup>9</sup>-tetrahydrocannabinol disrupts the intrasynaptic nanoscale stoichiometry and reduces synaptic variability. These findings imply that synapses leverage the nanoscale stoichiometry of presynaptic receptor coupling to the release machinery to establish synaptic strength in a target cell–dependent manner.</p>}},
  author       = {{Barti, Benjámin and Dudok, Barna and Kenesei, Kata and Zöldi, Miklós and Miczán, Vivien and Balla, Gyula Y. and Zala, Diana and Tasso, Mariana and Sagheddu, Claudia and Kisfali, Máté and Tóth, Blanka and Ledri, Marco and Sylvester Vizi, E. and Melis, Miriam and Barna, László and Lenkei, Zsolt and Soltész, Iván and Katona, István}},
  issn         = {{2375-2548}},
  language     = {{eng}},
  number       = {{22}},
  publisher    = {{American Association for the Advancement of Science (AAAS)}},
  series       = {{Science Advances}},
  title        = {{Presynaptic nanoscale components of retrograde synaptic signaling}},
  url          = {{http://dx.doi.org/10.1126/sciadv.ado0077}},
  doi          = {{10.1126/sciadv.ado0077}},
  volume       = {{10}},
  year         = {{2024}},
}