Plasticity of mouse enteric synapses mediated through endocannabinoid and purinergic signaling
Article first published online: 11 JAN 2012
© 2012 Blackwell Publishing Ltd
Neurogastroenterology & Motility
Volume 24, Issue 3, pages e113–e124, March 2012
How to Cite
Hons, I. M., Storr, M. A., Mackie, K., Lutz, B., Pittman, Q. J., Mawe, G. M. and Sharkey, K. A. (2012), Plasticity of mouse enteric synapses mediated through endocannabinoid and purinergic signaling. Neurogastroenterology & Motility, 24: e113–e124. doi: 10.1111/j.1365-2982.2011.01860.x
- Issue published online: 8 FEB 2012
- Article first published online: 11 JAN 2012
- Received: 13 July 2011 Accepted for publication: 14 December 2011
- enteric nervous system;
- retrograde transmission
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 CB1 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 CB1 deficient mice (CB1−/−) 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 CB1−/− neurons received spontaneous fast excitatory postsynaptic potentials than neurons from WT preparations. The CB1 agonist WIN55,212 depressed WT synapses without any effect on CB1−/− synapses. Synaptic activity in response to depolarization was markedly enhanced at CB1−/− synapses and after treatment with a CB1 antagonist in WT preparations. Activity-dependent liberation of a retrograde purine messenger was demonstrated to facilitate synaptic transmission in CB1−/− 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 CB1 receptors.