Coordination of airway protective behaviors and swallow: effects of afferent feedback and sex.

This dissertation represents a series of studies describing mechanisms related to breathing, upper airway behaviors and their coordination in man and animal. Chapter two transformed the cough swallow aspiration protocol from the cat (previous work) to the human introducing a new strategy, volume targeting, in swallow breathing coordination. Chapter three evaluated swallow breathing coordination at increasing altitudes. As respiratory drive altered due to hypoxia and hypocapnia, swallow breathing coordination shifted toward inspiration occurring during the transition from inspiration and expiration. The collection of the two previous studies led to development of an animal model to evaluate volume targeting and mechanisms involved in this strategy. Chapter four highlights presence of vagal spinal feedback on breathing characteristics and chapter five the same for swallow behavior and swallow breathing coordination. Chapter four and five also introduce sex differences in breathing and swallow breathing coordination when vagal and spinal balance is perturbed. In conclusion, this work has furthered the knowledge of swallow breathing coordination and suggested mechanisms responsible for these behaviors. Describing basic swallow parameters in human could lead to potential detection of pathologic changes in the upper airway as well as further the understanding of pulmonary complications such as aspiration pneumonia. The influence of the thoracic cavity spinal feedback could lead to new therapeutic techniques for breathing, swallow and their coordination in spinal cord injured patients

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Role of the postinspiratory complex in regulating swallow–breathing coordination and other laryngeal behaviors

Breathing needs to be tightly coordinated with upper airway behaviors, such as swallowing. Discoordination leads to aspiration pneumonia, the leading cause of death in neurodegenerative disease. Here, we study the role of the postinspiratory complex (PiCo) in coordinating breathing and swallowing. Using optogenetic approaches in freely breathing anesthetized ChATcre:Ai32, Vglut2cre:Ai32 and intersectional recombination of ChATcre:Vglut2FlpO:ChR2 mice reveals PiCo mediates airway protective behaviors. Activation of PiCo during inspiration or the beginning of postinspiration triggers swallow behavior in an all-or-nothing manner, while there is a higher probability for stimulating only laryngeal activation when activated further into expiration. Laryngeal activation is dependent on stimulation duration. Sufficient bilateral PiCo activation is necessary for preserving the physiological swallow motor sequence since activation of only a few PiCo neurons or unilateral activation leads to blurred upper airway behavioral responses. We believe PiCo acts as an interface between the swallow pattern generator and the preBötzinger complex to coordinate swallow and breathing. Investigating PiCo’s role in swallow and laryngeal coordination will aid in understanding discoordination with breathing in neurological diseases

Mapping the Time Course of Semantic Activation In Mediated False Memory: Immediate Classification, Naming, and Recognition

We evaluated the time course of persistent automatic spreading activation from a mediated list of indirect associates (e.g., meow, day, and basement) that all converged upon a non-presented critical item (CI; e.g., black). Mediated lists were related to CIs through non-presented mediators (e.g., cat, night, and bottom). Three speeded tasks were used to evaluate the time course of semantic activation of the CI: a continuous semantic classification task (concrete/abstract decisions), a naming task (reading words aloud), or a recognition test (old/new memory decisions). Test lists were presented immediately following the mediated lists, and CIs were presented in the first, third, or eighth positions. The results revealed that in both the classification and naming tasks, CI priming was greatest in the first test position and declined across the remaining test positions. Importantly, priming was statistically reliable in the late test positions, providing evidence for long-term semantic priming (i.e., across positions on immediate tasks). False recognition, however, was stable across test positions. Collectively, these patterns suggest that spreading-activation processes decline, consistent with implicit spreading activation, and these processes may contribute to long-term false recognition

Sex-specific vagal and spinal modulation of swallow and its coordination with breathing.

Swallow-breathing coordination is influenced by changes in lung volume, which is modulated by feedback from both vagal and spinal sensory afferents. The purpose of this study was to manipulate feedback from these afferents, with and without a simultaneous mechanical challenge (chest compression), in order to assess the influence of each sensory pathway on swallow in rats. We hypothesized that manipulation of afferent feedback would shift the occurrence of swallow toward the inspiratory phase of breathing. Afferent feedback was perturbed by lidocaine nebulization, extra-thoracic vagotomy, or lidocaine administration to the pleural space in sodium pentobarbital anesthetized rats (N = 43). These different afferent perturbations were performed both in control conditions (no chest compression), and with chest compression. Manipulating pulmonary stretch receptor-mediated volume feedback in male animals decreased swallow occurrence. Female rats appear to rely more on spinal afferent feedback, as swallow occurrence shifted to late expiration with chest compression and vagotomy or lidocaine injections. Results suggest that sex-specific mechanisms modulate swallow-breathing coordination, and that vagal feedback is inhibitory to swallow-related muscles, while spinal feedback from pleural afferents has excitatory effects. This study supports the theory that a balance of vagal and spinal afferent feedback is necessary to maintain an optimal swallow pattern and swallow-breathing coordination

Sex-specific vagal and spinal modulation of breathing with chest compression.

Lung volume is modulated by sensory afferent feedback via vagal and spinal pathways. The purpose of this study was to systematically alter afferent feedback with and without a mechanical challenge (chest compression). We hypothesized that manipulation of afferent feedback by nebulization of lidocaine, extra-thoracic vagotomy, or lidocaine administration to the pleural space would produce differential effects on the motor pattern of breathing during chest compression in sodium pentobarbital anesthetized rats (N = 43). Our results suggest that: 1) pulmonary stretch receptors are not the sole contributor to breathing feedback in adult male and female rats; 2) of our manipulations, chest compression had the largest effect on early expiratory diaphragm activity ("yield"); 3) reduction of spinally-mediated afferent feedback modulates breathing patterns most likely via inhibition; and 4) breathing parameters demonstrate large sex differences. Compared to males, female animals had lower respiratory rates (RR), which were further depressed by vagotomy, while chest compression increased RR in males, and decreased yield in females without changing RR. Collectively, our results suggest that balance between tonic vagal inhibition and spinal afferent feedback maintains breathing characteristics, and that it is important to specifically evaluate sex differences when studying control of breathing

The C Protein Is Recruited to Measles Virus Ribonucleocapsids by the Phosphoprotein

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