Serotonergic and glutamatergic neurons at the ventral medullary surface of the human infant: Observations relevant to central chemosensitivity in early human life

Auton Neurosci. 2006 Jan 30;124(1-2):112-24. doi: 10.1016/j.autneu.2005.12.009. Epub 2006 Feb 2.


Central chemoreception is the mechanism by which the brain detects the level of carbon dioxide (CO(2)) in the arterial blood and alters breathing accordingly in order to maintain it within physiological levels. The ventral surface of the medulla oblongata (VMS) of animals has long been recognized as a site of chemosensitivity, culminating in the recent identification of chemosensitive serotonergic (5-HT) and glutamatergic (Glut) neurons in this region. In this study, we analyzed the distribution of 5-HT and Glut neurons and their receptors in the arcuate nucleus (Arc) at the VMS of the human infant, using single-and double-label immunohistochemistry with specific antibodies. We also examined the expression of astrocytes, as experimental evidence suggests that astrocytes mediate, at least in part, central chemosensitivity via 5-HT and/or Glut receptors. We identified a small number of 5-HT neurons (approximately 5% of Arc neurons), distributed over the entire extent of the VMS, a large number of Glut neurons (approximately 95% of Arc neurons) that localized almost exclusively to the medial Arc, and a large number of astrocytes distributed across the entire extent of the VMS. The Arc also contained 5-HT(1A), kainate (GluR5), and 5-HT(2A) receptors, which localized predominantly to 5-HT neurons, glutamate neurons and astrocytes, respectively. Astrocytes also expressed the vesicular glutamate transporter 2 and low levels of 5-HT(1A) and kainate (GluR5) receptors, indicating that astrocytes may store and release glutamate, possibly in response to stimulation by 5-HT and/or Glut. These observations suggest that important functional interactions exist between 5-HT, glutamate, and astrocytes in the Arc. They also support the idea that the Arc is homologous to chemosensitive zones at the VMS in experimental animals. These data are important towards delineating the role of the human Arc in modulation of homeostasis, and its dysfunction in brainstem-associated pathologies such as the sudden infant death syndrome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arcuate Nucleus of Hypothalamus / cytology
  • Arcuate Nucleus of Hypothalamus / physiology
  • Astrocytes / metabolism
  • Astrocytes / physiology
  • Autoradiography
  • Chemoreceptor Cells / physiology*
  • Cytoskeletal Proteins / physiology
  • Female
  • Glial Fibrillary Acidic Protein / metabolism
  • Glutamic Acid / physiology*
  • Humans
  • Image Processing, Computer-Assisted
  • Immunohistochemistry
  • Infant
  • Infant, Newborn
  • Kainic Acid / metabolism
  • Lysergic Acid Diethylamide
  • Male
  • Medulla Oblongata / cytology
  • Medulla Oblongata / physiology*
  • Nerve Tissue Proteins / physiology
  • Neurons / physiology*
  • Paraffin Embedding
  • Radioligand Assay
  • Receptor, Serotonin, 5-HT1A / physiology
  • Receptor, Serotonin, 5-HT2A / physiology
  • Receptors, Kainic Acid / drug effects
  • Receptors, Kainic Acid / genetics
  • Receptors, Kainic Acid / physiology
  • Serotonin / physiology*
  • Serotonin Agents
  • Tryptophan Hydroxylase / metabolism
  • Vesicular Glutamate Transport Protein 2 / metabolism


  • Cytoskeletal Proteins
  • Glial Fibrillary Acidic Protein
  • Gluk1 kainate receptor
  • Nerve Tissue Proteins
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Kainic Acid
  • Serotonin Agents
  • Vesicular Glutamate Transport Protein 2
  • activity regulated cytoskeletal-associated protein
  • Receptor, Serotonin, 5-HT1A
  • Serotonin
  • Glutamic Acid
  • Lysergic Acid Diethylamide
  • Tryptophan Hydroxylase
  • Kainic Acid