title: Enteric glia are targets of the sympathetic innervation of the myenteric plexus in the guinea pig distal colon.
abstract: Astrocytes respond to synaptic activity in the CNS. Astrocytic responses are synapse specific and precisely regulate synaptic activity. Glia in the peripheral nervous system also respond to neuronal activity, but it is unknown whether glial responses are synapse specific. We addressed this issue by examining the activation of enteric glia by distinct neuronal subpopulations in the enteric nervous system. Enteric glia are unique peripheral glia that surround enteric neurons and respond to neuronally released ATP with increases in intracellular calcium ([Ca2+]i). Autonomic control of colonic function is mediated by intrinsic (enteric) and extrinsic (sympathetic, parasympathetic, primary afferent) neural pathways. Here we test the hypothesis that a defined population of neurons activates enteric glia using a variety of techniques to ablate or stimulate components of the autonomic innervation of the colon. Our findings demonstrate that, in the male guinea pig colon, activation of intrinsic neurons does not stimulate glial [Ca2+]i responses and fast enteric neurotransmission is not necessary to initiate glial responses. However, ablating extrinsic innervation significantly reduces glial responses to neuronal activation. Activation of primary afferent fibers does not activate glial [Ca2+]i responses. Selectively ablating sympathetic fibers reduces glial activation to a similar extent as total extrinsic denervation. Neuronal activation of glia follows the same frequency dependence as sympathetic neurotransmitter release, but the only sympathetic neurotransmitter that activates glial [Ca2+]i responses is ATP, suggesting that sympathetic fibers release ATP to activate enteric glia. Therefore, enteric glia discern activity in adjacent synaptic pathways and selectively respond to sympathetic activation.
authors.affiliation: Hotchkiss Brain Institute, Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta T2N 4N1, Canada. bgulbran@ucalgary.ca
authors.forename: Brian D
authors.initials: BD
authors.lastname: Gulbransen
authors.forename: Jaideep S
authors.initials: JS
authors.lastname: Bains
authors.forename: Keith A
authors.initials: KA
authors.lastname: Sharkey
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003106:Colon / Q000294:innervation* / Q000502:physiology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009197:Myenteric Plexus / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D018377:Neurotransmitter Agents; D011978:Receptors, Nicotinic; D000255:Adenosine Triphosphate; D002118:Calcium
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