Synaptic and membrane properties of parasympathetic ganglionic neurons innervating mouse trachea and bronchi

Abstract

The pathophysiology of airway diseases, such as asthma, is increasingly studied using transgenic mice and other mouse models of airway inflammation where allergen-induced changes in airway smooth muscle tone and mucous secretion is due, in part, to activation of preganglionic airway parasympathetic nerves. Ganglionic parasympathetic neurons located in the airways in several species, including humans, have anatomical and electrophysiological properties that limit transmission of preganglionic synaptic input. In this study, intracellular recordings were made from neurons in parasympathetic ganglia located on the trachea and bronchi of adult mice to determine electrophysiological properties associated with regulation of transmission of preganglionic input. Ganglionic neurons were characterized as having either tonic or phasic action potential accommodation patterns. Tonic neurons responded with repetitive action potentials sustained throughout a depolarizing current step, whereas phasic neurons generated one or a burst of action potential(s) and accommodated. A small subset displayed both patterns. Phasic neurons could be further differentiated as usually having either short- or long-duration afterhyperpolarizing potential following single and multiple action potentials. In most cells, stimulation of preganglionic nerves elicited one population of nicotinic fast excitatory postsynaptic potentials that were graded in amplitude, usually suprathreshold for action potential generation, and did not decrease in amplitude during higher frequency stimulation. Dye injection into the neurons revealed that dendrites were either absent or very short. These results provide evidence that in contrast to the characteristics of airway parasympathetic neurons reported in other species, including human, the electrophysiological and synaptic properties, and anatomical characteristics of mouse lower airway ganglionic neurons, are less associated with integration of presynaptic input.

The Effects of Nerve Growth Factor on Nicotinic Synaptic Transmission in Mouse Airway Parasympathetic Neurons

“…or after, NGF exposure (1-100 ng/ml; n = 4-6). As previously reported (18), the majority (63%) of mouse airway ganglioic neurons respond to a prolonged depolarizing pulse with a burst of action potentials followed by accommodation (phasic neurons), and the remaining neurons fire action potentials throughout the pulse (tonic neurons [18]). There was no significant change in the accommodation properties (tonic and phasic action potential patterns) by these neurons during a 2-minute application of 30 or 100 ng/ml of NGF (n = 5) or during 30-minute exposure (n = 4).…”

“…The trachea and bronchus were then cut longitudinally along the ventral midline, opened, and tightly pinned as a sheet, with the dorsal surface of the tissue facing upwards, to Sylgard (Dow Corning Corp., Midland, MI), which lined the floor of a recording chamber. Unstained ganglia were exposed in the trachea and bronchus by fine dissection with the aid of a stereomicroscope (Olympus America, Inc., Melville, NY) at magnifications of 25-803, using reflected transmitted light as previously described (18). Tracheal ganglia were located over the tracheal smooth muscle by following inlet nerves arising from the recurrent laryngeal nerves, and bronchial ganglia from the peribronchial nerves.…”

Airway smooth muscle in airway reactivity and remodeling: what have we learned?

“…Furthermore, beyond anatomical and immunohistochemical localization of nerve pathways, their functional aspects are also being explored. For example, one study (331) found that the level of integration by ganglionic parasympathetic neurons in the airway differs between species, an important point to consider when using transgenic and other models that may have a neurogenic component. Separately, in guinea pigs, a subset of esophageal neurons that express calretinin and ACh have been found to provide excitatory input to tracheal cholinergic ganglia and thus indirectly regulate airway tone (197).…”

A Shh/miR-206/BDNF Cascade Coordinates Innervation and Formation of Airway Smooth Muscle

“…Intrinsic neurons have cell bodies clustered along the smooth muscle stripe in the trachea and major bronchi (Myers et al, 1990; Undem et al, 1900; Weichselbaum and Sparrow, 1999; Tollet et al, 2001; Langsdorf et al, 2011). These neurons have short axons that innervate nearby targets (Weigand and Myers, 2010). In contrast, cell bodies of extrinsic neurons are located in jugular/nodose ganglia, dorsal root ganglia, and sympathetic ganglia, while their axons extend into the lung to innervate ASM and neuroendocrine cells (Adriaensen and Scheuermann, 1993; Canning, 2006).…”