Mapping of the Substrate for Production of Swallow and Cough Within the Rostral Nucleus of the Tractus Solitarius (NTS)/Paramedian Reticular Nucleus by Electrical Stimulation

Abstract

Swallow and cough are airway protective behaviors which are regulated via overlapping networks in the brainstem. However, it is not known if there are locations in the caudal brainstem which are capable of centrally stimulating both behaviors. To this end, a craniotomy was performed in sodium-pentobarbital anesthetized freely-breathing animals (n = 8). Electromyograms were recorded from upper airway and respiratory muscles to confirm swallow, cough, breathing, and other airway protective behaviors. Using a concentric monopolar electrode, a series of stimulations were performed across the dorsal brainstem. The electrode was systematically placed at points ranging laterally from 0.6 to 3.4 mm, and rostrally from 0 to 2.6 mm away from obex with a depth ranging from 0.5 to 4.0 mm from the surface of the brainstem. We were able to elicit swallow at 63 loci. Visual inspection of the receptive field indicated 2 sub-populations, and a k-means clustering analysis of these points centered them at stereotaxic coordinates (Lateral, Rostral, Depth) of [2.72, 1.82, 1.82] and [1.07, 0.78, 2.46]. In contrast, cough was only elicited in 1 animal at 8 locations in and around the NTS/paramedian reticular nucleus, with a cluster centered around [0.85, 0.53, 2.63]; these locations also elicited swallowing. These results are consistent with and extend early work of Sherrington (1915) and Markwald (1886). The neural substrate responsible for the production of swallow in this region of the medulla appears to be more expansive than that for cough. Our limited success in inducing cough with electrical stimulation in these areas is consistent with: a) a more anatomically distributed cough network relative to that for swallow, and/or b) more complex local synaptic mechanisms for induction of coughing that are resistant to actuation by electrical stimulation. An example of such a mechanism is selective inhibition of some neuron populations that are required to bring cough to threshold. In this case, frank excitation of these populations by electrical stimulation would have a limited effect in eliciting coughing.