The distribution of neurons in the rostral nucleus of the solitary tract (rNST) that respond to gustatory input from the anterior tongue was visualized by Fos protein immunohistochemistry following electrical stimulation of the chorda tympani (CT) nerve in rats. Maps of Fos-immunoreactive (Fos-ir) neurons were compared with the distribution of CT afferent terminal fields labeled by transganglionic transport of rhodamine-dextran in a separate group of animals. The primary concentration of Fos-ir neurons localized in register with the major terminal fields of CT afferent fibers, in the central third of the rostral 1.0 mm of the NST ipsilateral to the stimulated nerve. A similar correspondence in location and degree of labeling of Fos-ir neurons and afferent terminals was observed in the ipsilateral dorsal spinal trigeminal complex (Sp5) pars caudalis, near the obex, and the Sp5 pars oralis near the rostral pole of the rNST. Thus, the magnitude of Fos upregulation in brainstem targets of the CT nerve having chemosensory or nociceptive function, was proportional to the relative density of the CT afferent input. This correspondence, and the absence of labeling in neurons known to be one additional synapse away from the afferent input within gustatory or oral reflex pathways, suggests that the cell map obtained represents mainly neurons that are directly activated via primary afferent synapses from CT fibers. The availability of a method to histochemically identify a population of putative second-order taste neurons will facilitate analysis of the cellular/molecular properties of these neurons and of synaptic circuitry in the rNST.

No description available.

No description available.

HRP applied to cut dorsal and ventral roots of the cat sacral spinal cord labeled afferent axons with swellings in close apposition to labeled preganglionic neurons (PGNs) in the sacral parasympathetic nucleus. Electron microscopy allowed characterization of synaptic contacts between afferents and PGNs. The results suggest that both the dorsal and ventral root afferents can directly activate autonomic preganglionic neurons.

Thesis (Ph. D.)--University of Oklahoma. / Includes bibliographical references.

BACKGROUND:Migraine headache is one of the most common neurological disorders, but the pathophysiology contributing to migraine is poorly understood. Intracranial interleukin-6 (IL-6) levels have been shown to be elevated during migraine attacks, suggesting that this cytokine may facilitate pain signaling from the meninges and contribute to the development of headache.METHODS:Cutaneous allodynia was measured in rats following stimulation of the dura with IL-6 alone or in combination with the MEK inhibitor, U0126. The number of action potentials and latency to the first action potential peak in response to a ramp current stimulus as well as current threshold were measured in retrogradely-labeled dural afferents using patch-clamp electrophysiology. These recordings were performed in the presence of IL-6 alone or in combination with U0126. Association between ERK1 and Nav1.7 following IL-6 treatment was also measured by co-immunoprecipitation.RESULTS:Here we report that in awake animals, direct application of IL-6 to the dura produced dose-dependent facial and hindpaw allodynia. The MEK inhibitor U0126 blocked IL-6-induced allodynia indicating that IL-6 produced this behavioral effect through the MAP kinase pathway. In trigeminal neurons retrogradely labeled from the dura, IL-6 application decreased the current threshold for action potential firing. In response to a ramp current stimulus, cells treated with IL-6 showed an increase in the numbers of action potentials and a decrease in latency to the first spike, an effect consistent with phosphorylation of the sodium channel Nav1.7. Pretreatment with U0126 reversed hyperexcitability following IL-6 treatment. Moreover, co-immunoprecipitation experiments demonstrated an increased association between ERK1 and Nav1.7 following IL-6 treatment.CONCLUSIONS:Our results indicate that IL-6 enhances the excitability of dural afferents likely via ERK-mediated modulation of Nav1.7 and these responses contribute to migraine-related pain behavior in vivo. These data provide a cellular mechanism by which IL-6 in the meninges causes sensitization of dural afferents therefore contributing to the pathogenesis of migraine headache.

Swallowing is an essential motor act that coordinates the movement of food or saliva from the mouth through the pharynx and into the esophagus while protecting the upper airways from aspiration of those materials. Disordered swallowing, or dysphagia, results when bolus movement from the oropharyngeal phase into the esophageal phase is uncoordinated. Dysphagia directly causes or increases the risk of aspiration during swallowing in many clinical pathologies including Parkinson’s disease, Alzheimer’s disease, cerebrovascular incidents (stroke) in addition to being prevalent among the elderly population. The coordination between breathing and swallowing is mediated through the interaction of the swallow and respiratory Central Pattern Generators (CPGs) located in the brainstem. In the pharyngeal phase of swallow respiratory airflow is temporarily interrupted, and then reset, when the bolus moves through the pharyngeal space. The lungs retain enough air during the swallow apnea to protect the lower airways from accidental aspiration of residual bolus material, modulate the latency to initiate the swallow, while providing sensory feedback for processing within the brainstem network. The timing of the pharyngeal phase of swallow with respiration occurs across a continuum of lung volumes. Following swallow, the latency to initiate inspiration of the subsequent respiratory cycle increases. The swallow-mediated increase in cycle duration on respiration may depend upon the central processing of pulmonary afferents that may also affect reconfiguration of the respiratory CPG to express the swallow CPG. The peripheral and central mechanisms of swallow-breathing coordination remain poorly understood. Here, the relationship between central inspiratory output and the resultant mechanical inflation of the lungs was manipulated and dissociated to test the hypothesis that a centrally- and peripherally-mediated “swallow gate” coordinates swallow initiation with central respiratory activity and vagally-mediated pulmonary feedback. We obtained data from decerebrate adult cats of either sex that fully recovered from isoflurane anesthesia prior to the decerebration procedure. Fictive swallows were elicited using electrical stimulation of the superior laryngeal nerves (SLN) or injection of water (Water) into the pharyngeal cavity. Both stimuli were presented at random during the central respiratory cycle and/or the mechanical ventilation cycle. Mechanical ventilation was either triggered in-phase with phrenic discharge activity or it was set independent of phrenic discharge activity. These two modes of mechanical ventilation facilitated our ability to analyze the collective and individual effect of lower airway feedback on swallow-breathing coordination. The efferent discharge activities were recorded from the right hypoglossal (XII), left phrenic (Phr), left lumbar iliohypogastric (Lum) and right vagus (X) or the right recurrent laryngeal (RLN) nerves using silver bipolar hooked electrodes. All nerve activity was full-wave rectified, amplified, RC integrated (τ=200-500 ms) and low-pass filtered prior to analysis for effects on swallow-breathing coordination across stimulation-ventilation conditions. We observed post-inspiratory type (Post-I) and expiratory type (Exp) swallows that produced discrete effects on central respiratory rhythm across all conditions. The Post-I type swallows disturbed the duration and amplitude of preceding central inspiratory activity, without affecting the duration of central expiratory activity. The Exp type swallows prolonged central expiration but produced no effect on central inspiratory activity. We observed that lung inflation negatively modulated swallow initiation during fixed mechanical ventilation in the absence of central respiratory output, i.e., during central apnea. Most swallow elicited during central apnea initiated during periods of low lower airway afferent feedback. Collectively, these findings extend the role for lower airway feedback beyond its role as a provider of lung afferent surveillance and identifies lower airway feedback as a modulator of swallow-breathing coordination.

国立情報学研究所で電子化したコンテンツを使用している。

Thesis (Ph. D.)--Memorial University of Newfoundland, Faculty of Medicne, 2001. / Typescript. Includes bibliographical references (leaves 156-172).

Master of Science / Department of Kinesiology / Steven Copp / Mechanical and metabolic signals arising during skeletal muscle contraction reflexly increase sympathetic nerve activity and blood pressure (i.e., the exercise pressor reflex). In a rat model of simulated peripheral artery disease (PAD) in which a femoral artery is chronically (~72 hours) ligated, the mechanically-sensitive component of the exercise pressor reflex during 1 Hz dynamic contraction is exaggerated compared to that found in normal rats. Whether this is due to an enhanced acute sensitization of mechanoreceptors by metabolites produced during contraction or involves a chronic sensitization of mechanoreceptors is unknown. To investigate this issue, in decerebrate, unanesthetized rats we tested the hypothesis that the increases in mean arterial blood pressure (MAP) and renal sympathetic nerve activity (RSNA) during 1 Hz dynamic stretch are larger when evoked from a previously “ligated” hindlimb compared to those evoked from the contralateral “freely perfused” hindlimb. Dynamic stretch provided a mechanical stimulus in the absence of contraction-induced metabolite production that replicated closely the pattern of the mechanical stimulus present during dynamic contraction. We found that the increases in MAP (freely perfused: 14±1, ligated: 23±3 mmHg, p=0.02) and RSNA were significantly greater during dynamic stretch of the ligated hindlimb compared to the increases during dynamic stretch of the freely perfused hindlimb. These findings suggest that the exaggerated mechanically-sensitive component of the exercise pressor reflex found during dynamic muscle contraction in this rat model of simulated PAD involves a chronic sensitizing effect of ligation on muscle mechanoreceptors and cannot be attributed solely to acute contraction-induced metabolite sensitization.