Mechanical stress activates neurites and somata of myenteric neurons

Abstract

The particular location of myenteric neurons, sandwiched between the 2 muscle layers of the gut, implies that their somata and neurites undergo mechanical stress during gastrointestinal motility. Existence of mechanosensitive enteric neurons (MEN) is undoubted but many of their basic features remain to be studied. In this study, we used ultra-fast neuroimaging to record activity of primary cultured myenteric neurons of guinea pig and human intestine after von Frey hair evoked deformation of neurites and somata. Independent component analysis was applied to reconstruct neuronal morphology and follow neuronal signals. Of the cultured neurons 45% (114 out of 256, 30 guinea pigs) responded to neurite probing with a burst spike frequency of 13.4 Hz. Action potentials generated at the stimulation site invaded the soma and other neurites. Mechanosensitive sites were expressed across large areas of neurites. Many mechanosensitive neurites appeared to have afferent and efferent functions as those that responded to deformation also conducted spikes coming from the soma. Mechanosensitive neurites were also activated by nicotine application. This supported the concept of multifunctional MEN. 14% of the neurons (13 out of 96, 18 guinea pigs) responded to soma deformation with burst spike discharge of 17.9 Hz. Firing of MEN adapted rapidly (RAMEN), slowly (SAMEN), or ultra-slowly (USAMEN). The majority of MEN showed SAMEN behavior although significantly more RAMEN occurred after neurite probing. Cultured myenteric neurons from human intestine had similar properties. Compared to MEN, dorsal root ganglion neurons were activated by neurite but not by soma deformation with slow adaptation of firing. We demonstrated that MEN exhibit specific features very likely reflecting adaptation to their specialized functions in the gut.

Mechanosensitive Piezo Channels in the Gastrointestinal Tract

“…Several studies have reported distinct mechanosensitive responses in enteric neurons to tensile stress (stretch), compressive stress (volume injection, glass probe, or von Frey hair), shear stress, and cell swelling (hypoosmotic solutions) (Dong, Jiang, Dong, & Mittal, 2014; Hibberd, Zagorodnyuk, Spencer, & Brookes, 2012; Kugler et al, 2015; Kunze et al, 1999; Kunze, Clerc, Furness, & Gola, 2000; Kunze et al, 1998; Mayer & Wood, 1975; Mazzuoli & Schemann, 2009, 2012; Spencer & Smith, 2004). While these studies suggest roles in mechanosen-sitivity sensing and control of muscle activity, as well as a servo-feedback loop (Mazzuoli-Weber & Schemann, 2015), the identities of the mechano-sensitive ion channels responsible for mechanotransduction are largely unknown.…”

Intestinal Bacteria Maintain Adult Enteric Nervous System and Nitrergic Neurons via Toll-like Receptor 2-induced Neurogenesis in Mice

“…It has been assumed that such disorders may arise from injury or death of mature enteric neurons in what has traditionally been thought to be a static system with little or no capacity for renewal 4 . The ENS is continually exposed to a variety of extrinsic factors such as diet, mechanical stretch, medications, and toxins with recent data suggesting that many of these can influence the structure and function of ENS 5–9 . The mechanism through which these extrinsic factors can affect ENS are not fully understood, but the gut microbiota is emerging as one of the main mediators of these effects.…”

Stress, sex, and the enteric nervous system

“…13 Functionally, ENS neurons can be identified as motor neurons, intrinsic sensory or intrinsic primary afferent neurons, and interneurons, although different classes of interneurons are reported to have sensory functions, 15 while mechanosensitive neurites are shown to have afferent and efferent functions. 16 The ENS neurons code and use over 30 neurotransmitters/ mediators that are similar to those present in the central nervous system. 17 Cholinergic and nitrergic neurotransmissions are among the most abundant in the ENS and play key roles in the secretomotor, mucosal barrier, and immune responses of the human gut.…”