CELLULAR MECHANISMS OF MEDULLARY SEROTONERGIC NEURONS DURING DEVELOPMENT

$267,937P01FY2007HDNIH

Boston Children'S Hospital, Boston MA

Investigators

Linked publications & trials

Paper 38889800 Paper 38750089 Paper 38323418 Paper 37226597 Paper 33882306 Paper 32818601 Paper 31887304 Paper 31887303 Paper 31445030 Paper 31397480 Paper 30948838 Paper 30807103 Paper 30350781 Paper 30176250 Paper 30170082 Paper 28948999 Paper 28921675 Paper 28674018 Paper 28418237 Paper 28388601 Paper 28287253 Paper 28073937 Paper 27940805 Paper 27634962 Paper 27619736 Paper 27612489 Paper 27478061 Paper 27230764 Paper 27181326 Paper 27121960 Paper 27053202 Paper 26814804 Paper 26782962 Paper 26782961 Paper 26749015 Paper 26740230 Paper 26702023 Paper 26634772 Paper 26549332 Paper 26530629 Paper 26194567 Paper 26059034 Paper 25878157 Paper 25747116 Paper 25695895 Paper 25695656 Paper 25652113 Paper 25634430 Paper 25497093 Paper 25421424 Paper 25171790 Paper 24925912 Paper 24746050 Paper 24423636 Paper 24381267 Paper 24318835 Paper 23851109 Paper 23728974 Paper 23692315 Paper 23592597 Paper 23454177 Paper 23348024 Paper 23318703 Paper 23261662 Paper 23095976 Paper 22813968 Paper 22684039 Paper 22160541 Paper 22151329 Paper 21976671 Paper 21911619 Paper 21865888 Paper 21798952 Paper 21680874 Paper 21640183 Paper 21486799 Paper 21453797 Paper 21333760 Paper 21276877 Paper 21071595 Paper 20966190 Paper 20930126 Paper 20421636 Paper 20418346 Paper 20399912 Paper 20380898 Paper 20226279 Paper 20133433 Paper 20124538 Paper 20097312 Paper 19932690 Paper 19926534 Paper 19844731 Paper 19692691 Paper 19679071 Paper 19606910 Paper 19481178 Paper 19478196 Paper 19467322 Paper 19400695

Abstract

The overall goal of this program is to define the cause of SIDS. With the recent discovery of abnormal LSD binding in the medulla of SIDS infants, we have focused our efforts on the medullary serotonergic system, to define what specifically happens to serotonergic neurons to cause them to malfunction. The goal of Project 5 is to define the cellular properties of serotonergic neurons, as a means of providing a neurobiological explanation for the link between serotonin and SIDS. We have previously demonstrated that serotenergic neurons closely apposed to large arteries in the rat ventral medulla increase their firing rate in response to acidosis, and we have proposed that they are chemoreceptors that stimulete breathing, arousal and other CNS changes to restore pH homeostasis: We now plan to use a rat model to determine whether the cellular properties of serotonergic neurons can explain the three risk factors in the Triple Risk Model for SIDS. We wiil use a combination of multielectrode arrays and patch clamp recordings from serotonergic neurons in culture and in brain slices. We will: 1) Study how different subsets of serotonergic neuron respond to acidosis, hypoxia, temperature and glucose. 2) Examine how muscarinic receptor activation leads to enhancement of chemoreception. 3) Define the changes in chemosensitity of serotonergic neurons as they undergo development. 4) Determine the effects of acute and chronic (during pregnancy) nicotine exposure on the function of serotonergic neurons. 5) Compare the cellular properties of serotonergic neurons from rats with those of piglets and mice, and determine whether serotonergic neurons from these species, as well as human infants, are closely associated with large arteries of the ventral medulla. These experiments will provide information critical to a full understanding of the role of serotonergic neurons in brain function, and will lead to specific testable hypotheses about how their malfunction or maldevelopment could lead to death during sleep. URimately, the results of these experiments may provide important insights that could lead to diagnostic and therapeutic tests for those infants at highest risk of SIDS.

View original record on NIH RePORTER →