Back to Search
Start Over
Retrograde adenosine/A 2A receptor signaling facilitates excitatory synaptic transmission and seizures.
- Source :
-
Cell reports [Cell Rep] 2024 Jul 23; Vol. 43 (7), pp. 114382. Date of Electronic Publication: 2024 Jun 19. - Publication Year :
- 2024
-
Abstract
- Retrograde signaling at the synapse is a fundamental way by which neurons communicate and neuronal circuit function is fine-tuned upon activity. While long-term changes in neurotransmitter release commonly rely on retrograde signaling, the mechanisms remain poorly understood. Here, we identified adenosine/A <subscript>2A</subscript> receptor (A <subscript>2A</subscript> R) as a retrograde signaling pathway underlying presynaptic long-term potentiation (LTP) at a hippocampal excitatory circuit critically involved in memory and epilepsy. Transient burst activity of a single dentate granule cell induced LTP of mossy cell synaptic inputs, a BDNF/TrkB-dependent form of plasticity that facilitates seizures. Postsynaptic TrkB activation released adenosine from granule cells, uncovering a non-conventional BDNF/TrkB signaling mechanism. Moreover, presynaptic A <subscript>2A</subscript> Rs were necessary and sufficient for LTP. Lastly, seizure induction released adenosine in a TrkB-dependent manner, while removing A <subscript>2A</subscript> Rs or TrkB from the dentate gyrus had anti-convulsant effects. By mediating presynaptic LTP, adenosine/A <subscript>2A</subscript> R retrograde signaling may modulate dentate gyrus-dependent learning and promote epileptic activity.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Mice
Dentate Gyrus metabolism
Male
Receptor, trkB metabolism
Brain-Derived Neurotrophic Factor metabolism
Mice, Inbred C57BL
Hippocampus metabolism
Seizures metabolism
Seizures physiopathology
Receptor, Adenosine A2A metabolism
Adenosine metabolism
Signal Transduction
Synaptic Transmission physiology
Long-Term Potentiation physiology
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 43
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 38905101
- Full Text :
- https://doi.org/10.1016/j.celrep.2024.114382