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Plasticity of mouse enteric synapses mediated through endocannabinoid and purinergic signaling
Author(s) -
Hons I. M.,
Storr M. A.,
Mackie K.,
Lutz B.,
Pittman Q. J.,
Mawe G. M.,
Sharkey K. A.
Publication year - 2012
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.2011.01860.x
Subject(s) - neurotransmission , enteric nervous system , cannabinoid receptor , biology , synaptic plasticity , excitatory postsynaptic potential , postsynaptic potential , neuroscience , inhibitory postsynaptic potential , synaptic fatigue , receptor , agonist , biochemistry
Background The enteric nervous system (ENS) possesses extensive synaptic connections which integrate information and provide appropriate outputs to coordinate the activity of the gastrointestinal tract. The regulation of enteric synapses is not well understood. Cannabinoid (CB) 1 receptors inhibit the release of acetylcholine (ACh) in the ENS, but their role in the synapse is not understood. We tested the hypothesis that enteric CB 1 receptors provide inhibitory control of excitatory neurotransmission in the ENS. Methods Intracellular microelectrode recordings were obtained from mouse myenteric plexus neurons. Interganglionic fibers were stimulated with a concentric stimulating electrode to elicit synaptic events on to the recorded neuron. Differences between spontaneous and evoked fast synaptic transmission was examined within preparations from CB 1 deficient mice (CB 1 −/− ) and wild‐type (WT) littermate controls. Key Results Cannabinoid receptors were colocalized on terminals expressing the vesicular ACh transporter and the synaptic protein synaptotagmin. A greater proportion of CB 1 −/− neurons received spontaneous fast excitatory postsynaptic potentials than neurons from WT preparations. The CB 1 agonist WIN55,212 depressed WT synapses without any effect on CB 1 −/− synapses. Synaptic activity in response to depolarization was markedly enhanced at CB 1 −/− synapses and after treatment with a CB 1 antagonist in WT preparations. Activity‐dependent liberation of a retrograde purine messenger was demonstrated to facilitate synaptic transmission in CB 1 −/− mice. Conclusions & Inferences Cannabinoid receptors inhibit transmitter release at enteric synapses and depress synaptic strength basally and in an activity‐dependent manner. These actions help explain accelerated intestinal transit observed in the absence of CB 1 receptors.