Conditional Loss of Engrailed 1/2 in Rhombic Lip-Derived Neurons Increases Intrinsic Rhythmicity and Decreases Overall Variability of Eupneic Respiration

<p>Evidence for a cerebellar role during cardiopulmonary challenges has long been established, but investigation into cerebellar involvement in eupneic breathing has been inconclusive. Given the view of the cerebellum (CRB) as a temporally coordinating structure, any investigation into the CRB during respiration must evaluate rhythm and variability of the respiratory sequence. In this study, we chose an elegant model of cerebellar neuropathology, Atoh1-En1/2 CKO, where mutant animals have conditional loss of the developmental patterning gene Engrailed 1/2 in rhombic lip-lineage neurons and exhibit a proportional scaling-down of neuron number in hypoplastic lobules of the CRB. We utilized whole-body unrestrained plethysmography to measure respiration during eupnea, and evaluated the respiratory sequence of mutant animals and their control littermates using the average rate, the coefficient of variation (CV), and a unique measure of intrinsic rhythmicity called CV2. Linear regression analyses revealed that mutant animals had decreased overall variability and increased intrinsic rhythmicity (as measured by CV and CV2, respectively) compared to their control littermates, but we found no effect of strain on average respiratory rate. Analysis also revealed modestly decreased respiratory rates, increased CV, and increased CV2 in female animals, independent of strain. These results align well with previously reported studies and add new insight into CRB involvement in eupneic respiratory rhythmicity. Although not investigated in this study, future works should consider the coordination of breathing, licking, swallowing, and whisking in order to build a more complete understanding of the relationship between the CRB and respiration.</p>

Name thesis:degree_name

Master of Science (MS)

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Biomedical Sciences

Year dc:date.available

2020

Author dc:creator

• Taylor, Angela P.

Contributors dc:contributor

• Detlef H. Heck, PhD

• breathing
• cerebellum
• deep cerebellar nuclei
• engrailed
• mouse
• respiration
• Medical Cell Biology
• Medical Neurobiology
• Medical Physiology
• Medical Sciences
• Medicine and Health Sciences
• Neurosciences
• Physiological Processes

Repository record dc:identifier

https://dc.uthsc.edu/dissertations/541

OAI identifier oai:identifier

oai:dc.uthsc.edu:dissertations-1533