缅北强奸

Speaker:听Clifford. B. Saper

Department of Neurology, Program in Neuroscience, Beth Israel Deaconess Medical Center and Harvard Medical School,听USA

Registration available .听

础产蝉迟谤补肠迟:听Sleep apnea is caused by relaxation of the airway dilator muscles during sleep that causes the airway to become occluded. During the apnea, there is a rise in CO2, fall in O2, and increased negative airway pressure as the individual tries to breathe. These stimuli eventually cause arousal with wakening as well as sudden increase in muscle tone, opening the airway. The patient then falls asleep again, only to have this recur a few minutes later. We have traced the neural pathways taken by hypoxic, hypercarbic, and airway mechanoreceptors into the brain, and found that all of these converge on neurons in the ventrolateral part of the parabrachial nucleus (PB) in the pons. The PB neurons that are activated by hypoxia or hypercarbia are glutamatergic, and we found that deleting the vesicular glutamate transporter 2 gene from them prevents arousals to these stimuli. In a molecular dissection of the PB, we found that the neurons activated by hypercarbia that project to the forebrain express calcitonin gene-related peptide (CGRP). Optogenetic inhibition of just the CGRP neurons in the PB or their targets in the forebrain caused loss of awakening to CO2, although stimulation of respiration remained intact, suggesting that the respiratory and arousal components of CO2 response are mediated by different neurons.

Other work had suggested that the serotonin system is also required for CO2 response. We found that the serotonin input to the CGRP neurons comes from the dorsal raphe nucleus. Optogenetic inhibition of the dorsal raphe serotonin neurons or their terminals in the PB prevented arousal to CO2, but not respiratory response. PB CGRP neurons were found to express 5HT2a receptors for serotonin, and when animals were given a 5HT2a agonist, inhibition of the dorsal raphe no longer prevented arousal to CO2. Thus the effect of the serotonin system on CO2 arousal is due to dorsal raphe inputs to the PB CGRP cells. However, this pathway has little effect on the respiratory response to CO2.

We next looked for genetic markers that define the PB neurons that contribute to the respiratory response to CO2. We found that neurons that express the FoxP2 transcription factor send efferents to the respiratory control centers in the medulla, and show increased activity with fiber photometry during CO2 exposure. Optogenetic activation of these neurons selectively increases respiration, while photoinhibition causes a reduction in CO2 stimulated ventilation, but not in awakening to CO2.

We are currently studying single cell expression profiling in the PB to determine which genetically defined classes of cells contribute to the wakening and ventilatory responses to CO2, and whether differences in receptor expression may permit differential reduction in awakening and increased respiratory response in patients with sleep apnea, thus limiting sleep fragmentation and periods of hypoxia.

Supported by the generosity of the Killam Trusts , The Neuro鈥檚 Killam Seminar series hosts outstanding guest speakers whose research is of interest to the scientific community at The Neuro and 缅北强奸.