The Enteric Innervation and It’s Pancreatic Projections

Our group is concerned with understanding the microcircuits that comprise the enteric nervous system (ENS) and pancreas, to better understand the neural regulation of gastrointestinal motility and pancreatic secretion.

Our laboratory is studying the physiology of enteropancreatic reflexes and the intrinsic circuity of the gut and pancreas. The enteric nervous system (ENS), the intrinsic innervation of the gut, is the only organ of the body that can mediate reflex activity independently of an innervation from the CNS. The ENS also innervates other organs, including the pancreas (Kirchgessner and Gershon, 1990). Pancreatic ganglia are similar to enteric ganglia, and are the primary target of the enteric innervation. When enteric neurons are stimulated, neurons in pancreatic ganglia, as well as the islet and acinar cells they innervate, are activated. Our goals are to understand the neural organizations of enteropancreatic reflexes, and to determine how the intrinsic innervation of the pancreas controls insulin (and amylase) secretion. Combining retrograde tracing with electrophysiology, intracellular dye-filling and immunocytochemistry, allows us to determine which pancreatic neurons actually project to the islets, to define their characteristics, and to identify their function.

Our work on the physiology of enteropancreatic reflexes is supplemented by the cellular biology of one of the neurons of enteric ganglia, the glutamatergic neuron. Current work involves characterization of enteric glutamate (ionotropic and metabotropic) receptors, regulation of glutamate release, and studies on the role of glutamate in the peristaltic reflex. A variety of techniques are used in these studies, including intracellular and patch clamp recording, Ca²⁺ imaging, in situ hybridization, and RT-PCR.

Figure 1. Agonist-induced internalization of metabotropic glutamate receptor 5 in dissociated myenteric neurons.

Figure 2. Enteric neurons immunoselected with antibodies to nicotinic acetylcholine receptors (mab35) Receptor immunoreactivity (red) is differentially localized in enteric motorneurons (arrow) and putative primary afferent neurons identified by calbindin immunoreactivity (green).

Selected Publications

Kirchgessner, A. L., Liu, M. T., and Alcantara, F. (1997). Excitotoxicity in the enteric nervous system. J. Neurosci. 17, 8804-8816.

Kirchgessner, A. L., and Liu, M. T. (1999). Orexin synthesis and response in the gut. Neuron 24, 941-951.

Liu, M. T., Seino, S., and Kirchgessner, A. L. (1999). Identification and characterization of glucoresponsive neurons in the enteric nervous system. J. Neurosci. 19, 10305-10317.

Liu, M. T., and Kirchgessner, A. L. ( 2000). Agonist- and reflex-evoked internalization of metabotropic glutamate receptor 5 in enteric neurons. J. Neurosci. 20, 3200-3205.

Kirchgessner, A. L., and Liu, M. T. (2001). PACAP in the enteropancreatic innervation. Anat. Rec. 262, 91-100.

 
Personnel

Wei-ping Chen, M.D., Postdoctoral Associate

Raogo Ouedraogo, Ph.D., Postdoctoral Associate

Jie Ma, M.D., Graduate Student

Qingchun Tong, M.S., Graduate Student

 
Service Functions

Reviewer for various scientific journals and funding organizations.

  

            E-mail : akirchgessner@downstate.edu

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