1. Postsynaptic Pannexin-1 Facilitates Anandamide Uptake to Modulate Glutamate Release and Enhance Network Excitability
- Author
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Robinson Jh, Allison C. Werner, Pedro Grandes, Egaña J, Alexander W. Lohman, Gordon Campbell Teskey, Haley A. Vecchiarelli, Nicholas L. Weilinger, Jennifer Bialecki, Roger J. Thompson, Medizabal-Zubiaga J, and Matthew N. Hill
- 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 - 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.
- Published
- 2018