Orchestration of neuronal migration by activity of ion channels, neurotransmitter receptors, and intracellular Ca2+ fluctuations

J Neurobiol. 1998 Oct;37(1):110-30.

Abstract

The real-time observation of cell movement in acute cerebellar slices reveals that granule cells alter their shape concomitantly with changes in the mode and rate of migration as they traverse different cortical layers. Although the origin of local environmental cues responsible for these position-specific changes in migratory behavior remains unclear, several signaling mechanisms involved in controlling granule cell movement have emerged. The onset of one such mechanism is marked by the expression of voltage-gated ion channels and neurotransmitter receptors in postmitotic cells prior to the initiation of their migration. Granule cells start their radial migration after the expression of N-type Ca2+ channels and the N-methyl-D-aspartate subtype of glutamate receptors on the plasmalemmal surface. Blockade of the channel or receptor activity significantly decreases the rate of cell movement, indicating that the activation of these membrane constituents provides an essential signal for the translocation of granule cells. Another signal that controls the rate of cell migration is embedded in the combined amplitude and frequency components of Ca2+ fluctuations in the somata of migrating granule cells. Interestingly, each phase of Ca2+ fluctuation controls a separate phase of saltatory movement in the granule cells: The cells move forward during the phase of transient Ca2+ elevation and remain stationary during the troughs. Consequently, the changes in the amplitude and frequency components of Ca2+ fluctuations directly affect granule cell movement: Reducing the amplitude or frequency of Ca2+ fluctuations slows down the speed of cell movement, while the enhancement of these components accelerates migration. These findings suggest that signaling molecules present in the local cellular milieu encountered on the migratory route control the shape and motility of granule cells by modifying Ca2+ fluctuations in the soma through the activation of specific ion channels and neurotransmitter receptors.

Publication types

  • Review

MeSH terms

  • Animals
  • Calcium Channels / physiology*
  • Calcium Signaling / physiology*
  • Cell Movement*
  • Cell Size
  • Cerebellar Cortex / cytology*
  • Cerebellar Cortex / embryology
  • Neuroglia / physiology
  • Neurons / cytology
  • Neurons / physiology*
  • Purkinje Cells / metabolism
  • Receptors, N-Methyl-D-Aspartate / physiology*

Substances

  • Calcium Channels
  • Receptors, N-Methyl-D-Aspartate