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Postsynaptic Pannexin-1 Facilitates Anandamide Uptake to Modulate Glutamate Release and Enhance Network Excitability
- Publication Year :
- 2018
- Publisher :
- Cold Spring Harbor Laboratory, 2018.
-
Abstract
- Prolonged neurotransmitter release following synaptic stimulation extends the time window for postsynaptic neurons to respond to presynaptic activity. This can enhance excitability and increase synchrony of outputs, but the prevalence of this at normally highly synchronous synapses is unclear. We show that the postsynaptic channel, pannexin-1 (Panx1) regulates prolonged glutamate release onto CA1 neurons. Block of postsynaptic (CA1 neuronal) Panx1 increased the frequency of glutamate neurotransmission and action potentials in these neurons following Schaffer collateral stimulation. When Panx1 was blocked, anandamide levels increase and activated transient receptor potential vanilloid 1 (TRPV1)-mediated glutamate release. This TRPV1-induced synaptic acitvity enhanced excitability and translated into a faster rate of TRPV1-dependent epileptogenesis induced by kindling. We conclude that Panx1 facilitates AEA clearance to maintain synchronous release onto CA1 neurons so that when AEA clearance is reduced, TRPV1 channels prolong glutamate neurotransmission to enhance network output to promote epileptiform activity.
- Subjects :
- 0303 health sciences
musculoskeletal, neural, and ocular physiology
Glutamate receptor
TRPV1
Neurotransmission
Epileptogenesis
03 medical and health sciences
Transient receptor potential channel
chemistry.chemical_compound
0302 clinical medicine
medicine.anatomical_structure
nervous system
chemistry
Schaffer collateral
Postsynaptic potential
medicine
lipids (amino acids, peptides, and proteins)
Neurotransmitter
Neuroscience
030217 neurology & neurosurgery
030304 developmental biology
Subjects
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....d55236a345cdb9c36ba58dfcf44d13e7