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Medullary serotonin neurons are CO2 sensitive in situ
Journal article   Open access   Peer reviewed

Medullary serotonin neurons are CO2 sensitive in situ

Kimberly E Iceman, George B Richerson and Michael B Harris
Journal of neurophysiology, Vol.110(11), pp.2536-2544
12/2013
DOI: 10.1152/jn.00288.2013
PMCID: PMC3882770
PMID: 24047906
url
https://doi.org/10.1152/jn.00288.2013View
Published (Version of record) Open Access

Abstract

Brainstem central chemoreceptors are critical to the hypercapnic ventilatory response, but their location and identity are poorly understood. When studied in vitro, serotonin-synthesizing (5-HT) neurons within the rat medullary raphé are intrinsically stimulated by CO2/acidosis. The contributions of these neurons to central chemosensitivity in vivo, however, are controversial. Lacking is documentation of CO2-sensitive 5-HT neurons in intact experimental preparations and understanding of their spatial and proportional distribution. Here we test the hypothesis that 5-HT neurons in the rat medullary raphé are sensitive to arterial hypercapnia. We use extracellular recording and hypercapnic challenge of spontaneously active medullary raphé neurons in the unanesthetized in situ perfused decerebrate brainstem preparation to assess chemosensitivity of individual cells. Juxtacellular labeling of a subset of recorded neurons and subsequent immunohistochemistry for the 5-HT-synthesizing enzyme tryptophan hydroxylase (TPH) identify or exclude this neurotransmitter phenotype in electrophysiologically characterized chemosensitive and insensitive cells. We show that the medullary raphé houses a heterogeneous population, including chemosensitive and insensitive 5-HT neurons. Of 124 recorded cells, 16 cells were juxtacellularly filled, visualized, and immunohistochemically identified as 5-HT synthesizing, based on TPH-immunoreactivity. Forty-four percent of 5-HT cells were CO2 stimulated (increased firing rate with hypercapnia), while 56% were unstimulated. Our results demonstrate that medullary raphé neurons are heterogeneous and clearly include a subset of 5-HT neurons that are excited by arterial hypercapnia. Together with data identifying intrinsically CO2-sensitive 5-HT neurons in vitro, these results support a role for such cells as central chemoreceptors in the intact system.
Serotonergic Neurons - physiology Rats Male Chemoreceptor Cells - physiology Serotonergic Neurons - classification Raphe Nuclei - cytology Carbon Dioxide - blood Rats, Sprague-Dawley Action Potentials Medulla Oblongata - cytology Animals Raphe Nuclei - physiology Medulla Oblongata - physiology

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