Retrograde adenosine/A2A receptor signaling facilitates excitatory synaptic transmission and seizures.
Cell Rep
; 43(7): 114382, 2024 Jul 23.
Article
in En
| MEDLINE
| ID: mdl-38905101
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/A2A receptor (A2AR) 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 A2ARs were necessary and sufficient for LTP. Lastly, seizure induction released adenosine in a TrkB-dependent manner, while removing A2ARs or TrkB from the dentate gyrus had anti-convulsant effects. By mediating presynaptic LTP, adenosine/A2AR retrograde signaling may modulate dentate gyrus-dependent learning and promote epileptic activity.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Seizures
/
Signal Transduction
/
Adenosine
/
Long-Term Potentiation
/
Synaptic Transmission
/
Receptor, Adenosine A2A
Limits:
Animals
Language:
En
Journal:
Cell Rep
/
Cell reports
Year:
2024
Document type:
Article
Affiliation country:
Estados Unidos
Country of publication:
Estados Unidos