Chemosensitivity of serotonergic neurons in the rostral ventral medulla.
ABSTRACT The medullary raphé contains two subtypes of chemosensitive neuron: one that is stimulated by acidosis and another that is inhibited. Both types of neuron are putative chemoreceptors, proposed to act in opposite ways to modulate respiratory output and other pH sensitive brain functions. In this review, we will discuss the cellular properties of these chemosensitive raphé neurons when studied in vitro using brain slices and primary dissociated cell culture. Quantification of chemosensitivity of raphé neurons indicates that they are highly sensitive to small changes in extracellular pH (pH(o)) between 7.2 and 7.6. Stimulation by acidosis occurs only in the specific phenotypic subset of neurons within the raphé that are serotonergic. These serotonergic neurons also have other properties consistent with a specialized role in chemoreception. Homologous serotonergic neurons are present within the ventrolateral medulla (VLM), and may have contributed to localization of respiratory chemoreception to that region. Chemosensitivity of raphé neurons increases in the postnatal period in rats, in parallel with development of respiratory chemoreception in vivo. An abnormality of serotonergic neurons of the ventral medulla has been identified in victims of sudden infant death syndrome (SIDS). The cellular properties of serotonergic raphé neurons suggest that they play a role in the CNS response to hypercapnia, and that they may contribute to interactions between the sleep/wake cycle and respiratory control.
Article: The expanded biology of serotonin.[show abstract] [hide abstract]
ABSTRACT: Serotonin is perhaps best known as a neurotransmitter that modulates neural activity and a wide range of neuropsychological processes, and drugs that target serotonin receptors are used widely in psychiatry and neurology. However, most serotonin is found outside the central nervous system, and virtually all of the 15 serotonin receptors are expressed outside as well as within the brain. Serotonin regulates numerous biological processes including cardiovascular function, bowel motility, ejaculatory latency, and bladder control. Additionally, new work suggests that serotonin may regulate some processes, including platelet aggregation, by receptor-independent, transglutaminase-dependent covalent linkage to cellular proteins. We review this new "expanded serotonin biology" and discuss how drugs targeting specific serotonin receptors are beginning to help treat a wide range of diseases.Annual review of medicine 02/2009; 60:355-66. · 9.94 Impact Factor
[show abstract] [hide abstract]
ABSTRACT: Despite widespread prevalence of sleepwalking, its etiology and pathophysiology are not well understood. However, there is some evidence that sleepwalking can be precipitated by sleep-disordered breathing. A hypothesis is proposed that serotonergic system may be a link between sleep-disordered breathing and sleepwalking. Serotonergic neurons meet basic requirements for such a role because they are activated by hypercapnia, provide a tonic excitatory drive that gates afferent inputs to motoneurons, and the activity of serotonergic neurons can be dissociated from the level of arousal. This paper discusses also drug-induced somnambulism and co-occurrence of sleepwalking and other disorders such as migraine and febrile illness.Medical Hypotheses 02/2005; 64(1):28-32. · 1.39 Impact Factor
Article: BDNF is necessary and sufficient for spinal respiratory plasticity following intermittent hypoxia.[show abstract] [hide abstract]
ABSTRACT: Intermittent hypoxia causes a form of serotonin-dependent synaptic plasticity in the spinal cord known as phrenic long-term facilitation (pLTF). Here we show that increased synthesis of brain-derived neurotrophic factor (BDNF) in the spinal cord is necessary and sufficient for pLTF in adult rats. We found that intermittent hypoxia elicited serotonin-dependent increases in BDNF synthesis in ventral spinal segments containing the phrenic nucleus, and the magnitude of these BDNF increases correlated with pLTF magnitude. We used RNA interference (RNAi) to interfere with BDNF expression, and tyrosine kinase receptor inhibition to block BDNF signaling. These disruptions blocked pLTF, whereas intrathecal injection of BDNF elicited an effect similar to pLTF. Our findings demonstrate new roles and regulatory mechanisms for BDNF in the spinal cord and suggest new therapeutic strategies for treating breathing disorders such as respiratory insufficiency after spinal injury. These experiments also illustrate the potential use of RNAi to investigate functional consequences of gene expression in the mammalian nervous system in vivo.Nature Neuroscience 02/2004; 7(1):48-55. · 15.53 Impact Factor