Evaluating a Raphé Chemosensory Amplifier Network with Multi-Channel Array Recording

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DESCRIPTION (provided by applicant): Knowledge of the neurons with which the brain detects and responds to changes in CO2/pH (central chemosensitivity) is critical to understanding both homeostatic regulation and the nature of diseases resulting from failures in chemosensitivity, such as sleep apnea, Congenital Central Hypoventilation Syndrome and the Sudden Infant Death Syndrome. Medullary raphe neurons synthesizing the neurotransmitter serotonin (5HT) or γ-aminobutyric acid (GABA) are proposed as 1st order chemosensory neurons. Unknown, however, are the critical potential reciprocal interactions between 1st order neurons, and the role of 2nd order chemosensory neurons that may integrate, amplify and coordinate activities of 1st order neurons, to modulate homeostatic reflex responses to chemosensory stimuli. We postulate that 1st order raphé 5HT and GABA chemosensory neurons interact between themselves and drive a specific population of 2nd order neurons. Together, these form a local raphé chemosensory amplifier (RCA) network. Our overarching hypothesis is that 1st order sensory neurons of the medullary raphé are integrated by reciprocal interactions and 2nd order neurons to form a local coordinated network. We have two aims. Specific Aim 1: Intrinsic sensitivity of raphé 5HT and GABA neurons is shaped by the RCA network. Specific Aim 2: RCAI integrate and amplify inputs from 1st order 5HT and/or GABA neurons. Proposed studies will confirm and localize, or refute the existence of critical network interactions within the raphé influencing chemo responsiveness of neurons when within an intact nervous system. Results will test the validity of the RCA model, and will suggest an organization of the raphé chemosensory system and advance the understanding of central chemoreception by contributing definitive information about the network characteristics involved in this vital process.