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    The role of serotonergic (5-HT) neuromodulation in respiratory chemosensitivity

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    Author
    Fieldman, Deborah M.
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    URI
    http://hdl.handle.net/11122/5897
    Abstract
    Breathing 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.
    Description
    Thesis (M.S.) University of Alaska Fairbanks, 2007
    Table of Contents
    1. 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.
    Date
    2007-05
    Type
    Thesis
    Collections
    Biological Sciences

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