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This Article Full Text Full Text (PDF) All Versions of this Article: 586/9/2321    most recent jphysiol.2008.152231v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Li, A. Articles by Nattie, E. PubMed PubMed Citation Articles by Li, A. Articles by Nattie, E. Related Collections Respiratory

¹ Department of Physiology, Dartmouth Medical School, Lebanon, NH 03756-0001, USA

Medullary serotonergic (5-HT) neurons are implicated in central chemoreception and 5-HT abnormalities are present in many cases of the sudden infant death syndrome (SIDS). Mice with a targeted disruption of the serotonin transporter (5-HTT) develop in the presence of excess 5-HT in brain extracellular fluid (ECF). As adults they exhibit reduced 5-HT neuron activity and 5-HT_1A receptor binding with varying changes in postsynaptic 5-HT receptor function. They exhibit behavioural phenotypes (anxiety, reduced aggression) but little is known about their control of breathing. We show that conscious adult male and female 5-HTT knockout mice breathing air at room temperature have a higher resting , breathing frequency and but a normal body temperature and ratio (the ventilatory equivalent) compared to wild-type (WT) controls. In hypercapnia, there is a reduced ventilatory response (expressed as the ratio) that is much more prominent in males (–68%) than females (–22%). In hypoxia, both males and females exhibit a higher , and body temperature but their ratio is normal. We conclude that 5-HTT knockout mice have a diminished function of the medullary 5-HT system, which is manifest most remarkably in a substantial loss of CO₂ sensitivity predominantly in males. This finding supports the importance of medullary 5-HT neurons in central chemoreception. Females either rely less on 5-HT neurons in chemoreception or adapt more readily to the loss of 5-HT function. This genetic model allows examination of the role of excess 5-HT in ECF in the development of the control of breathing and central chemoreception, which may be pertinent to SIDS.

(Received 7 February 2008; accepted after revision 20 March 2008; first published online 20 March 2008)
Corresponding authors A. Li and E. Nattie: Department of Physiology, Dartmouth Medical School, Lebanon, NH 03756-0001, USA. Email: aihua.li{at}dartmouth.edu and eugene.nattie{at}dartmouth.edu