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dc.contributor.authorFieldman, Deborah M.
dc.date.accessioned2015-09-01T01:10:25Z
dc.date.available2015-09-01T01:10:25Z
dc.date.issued2007-05
dc.identifier.urihttp://hdl.handle.net/11122/5897
dc.descriptionThesis (M.S.) University of Alaska Fairbanks, 2007en_US
dc.description.abstractBreathing must be regulated to maintain appropriate levels of oxygen and carbon dioxide. Breathing may be influenced by serotonergic (5-HT) neurons, sensitive to CO₂, which activate the brain's respiratory network. However, this role of 5-HT neurons as CO₂-sensitive chemoreceptors in unanesthetized animals is unclear. This study used an unanesthetized in situ perfused rat brainstem preparation to test the hypothesis that 5-HT neurons contribute to CO₂ ventilatory responses. Changes in phrenic nerve discharge patterns were monitored as gas-saturated solutions supplying the preparation were switched from 5%C0₂ to 7%C0₂ (balance 0₂). The importance of 5-HT neurons was identified by comparing responses before and after application of the specific serotonin 1A receptor agonist 8-hydroxy-(dipropylamino) tetralin hydrobromide (8-OH-DPAT; at doses of 0, 1.5, 3, and 6 uM in the perfusate). The action of 8-OH-DPAT is to inhibit 5-HT neurons and reduce synaptic 5-HT release. Results indicated that changes in phrenic burst pattern similar to hypercapnic ventilatory responses observed in vivo, were greatly disrupted by 8-OH-DPAT treatment. These results illustrate that activation of 5-HT neurons is critical for CO₂ chemosensitivity in this in situ preparation and suggest that these neurons may play a key role in the regulation of breathing in otherwise intact animals.en_US
dc.description.tableofcontents1. Neural control of breathing -- 1.1. Respiratory pattern generation -- 1.2. Neuromodulation and chemosensitivity -- 1.3. Serotonergic neurons and chemosensitivity -- 1.3.1. Chemosensitivity of serotonergic neurons -- 1.3.2. Location -- 1.3.3. Connectivity -- 1.3.4. Serotonergic neuromodulation -- 1.4. 5-HT₁a receptors -- 1.5. Chemoreceptor controversy -- 1.6. Hypothesis -- 2. Materials and methods -- 2.1. Perfused rat brainstem preparation -- 2.2. Recording of neural activity -- 2.3. Protocol -- 2.4. Responses to hypercapnia -- 2.5. Responses to hypercapnia following serotonin block -- 2.6. Data analysis -- 3. Results -- 3.1. Initial conditions -- 3.2. Hypercapnic response -- 3.3. Time controls -- 3.4. Dose dependant response -- 3.5. Influence of 8-OH-DPAT -- 4. Conclusion -- 4.1. Eupnea -- 4.2. Frequency and Te increase with hypercapnia -- 4.3. Effect of 8-OH-DPAT on burst pattern during normocapnia -- 4.4. Effect of 8-OH-DPAT on respiratory response -- 4.5. Mechanisms -- References.en_US
dc.language.isoen_USen_US
dc.titleThe role of serotonergic (5-HT) neuromodulation in respiratory chemosensitivityen_US
dc.typeThesisen_US
dc.type.degreemsen_US
dc.identifier.departmentDepartment of Biology and Wildlifeen_US
refterms.dateFOA2020-03-13T01:24:54Z


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