Early serotonergic projections to Cajal-Retzius cells: relevance for cortical development

J Neurosci. 2004 Feb 18;24(7):1652-9. doi: 10.1523/JNEUROSCI.4651-03.2004.

Abstract

Although the serotonergic system plays an important role in various neurological disorders, the role of early serotonergic projections to the developing cerebral cortex is not well understood. Because serotonergic fibers enter the marginal zone (MZ) before birth, it has been suggested that they may influence cortical development through synaptic contacts with Cajal-Retzius (CR) cells. We used immunohistochemistry combined with confocal and electron microscopy to show that the earliest serotonergic projections to the MZ form synaptic contacts with the somata and proximal dendrites of CR cells as early as embryonic day 17. To elucidate the functional significance of these early serotonergic contacts with CR cells, we perturbed their normal development by injecting pregnant mice with 5-methoxytryptamine. Lower reelin levels were detected in the brains of newborn pups from the exposed animals. Because reelin plays an important role in the cortical laminar and columnar organization during development, we killed some pups from the same litters on postnatal day 7 and analyzed their presubicular cortex. We found that the supragranular layers of the presubicular cortex (which normally display a visible columnar deployment of neurons) were altered in the treated animals. Our results suggest a mechanism of how serotonergic abnormalities during cortical development may disturb the normal cortical organization; and, therefore, may be relevant for understanding neurological disorders in which abnormalities of the serotonergic system are accompanied by cortical pathology (such as autism).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 5-Methoxytryptamine / pharmacology
  • Animals
  • Axons / ultrastructure
  • Cell Adhesion Molecules, Neuronal / biosynthesis
  • Cell Adhesion Molecules, Neuronal / blood
  • Cerebral Cortex / cytology*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / embryology*
  • Cerebral Cortex / metabolism
  • Dendrites / ultrastructure
  • Extracellular Matrix Proteins / biosynthesis
  • Extracellular Matrix Proteins / blood
  • Female
  • Gestational Age
  • Mice
  • Nerve Tissue Proteins
  • Nervous System Malformations / chemically induced
  • Nervous System Malformations / pathology
  • Neurons / cytology*
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / ultrastructure
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Reelin Protein
  • Serine Endopeptidases
  • Serotonin / metabolism*
  • Synapses / ultrastructure

Substances

  • Cell Adhesion Molecules, Neuronal
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • Reelin Protein
  • Serotonin
  • 5-Methoxytryptamine
  • Reln protein, mouse
  • Serine Endopeptidases