Artificial CSF motion ensures rhythmic activity in the developing CNS ex vivo: a mechanical source of rhythmogenesis?

J Neurosci. 2011 Jun 15;31(24):8832-40. doi: 10.1523/JNEUROSCI.1354-11.2011.

Abstract

Spontaneous rhythmic activity is a ubiquitous feature of developing neural structures that has been shown to be essential for the establishment of functional CNS connectivity. However, the primordial origin of these rhythms remains unknown. Here, we describe two types of rhythmic activity in distinct parts of the developing CNS isolated ex vivo on microelectrode arrays, the expression of which was found to be strictly dependent upon the movement of the artificial CSF (aCSF) flowing over the inner wall of the ventricles or over the outer surface of the CNS. First, whole embryonic mouse hindbrain-spinal cord preparations (stages E12.5-E15.5) rhythmically expressed waves of activity originating in the hindbrain and propagating in the spinal cord. Interestingly enough, the frequency of this rhythm was completely determined by the speed of the aCSF flow. In particular, at all stages considered, hindbrain activity was abolished when the perfusion was stopped. Immature rhythmic activity was also recorded in the isolated newborn (P0-P8) mouse cortex under normal aCSF perfusion. Again, this rhythm was abolished when the perfusion flow was stopped. In both structures, this phenomenon was not due to changes in temperature, oxygen level, or pH of the bath, but to the movement itself of the aCSF. These observations challenge the so-called "spontaneous" nature of rhythmic activity in immature neural networks and suggest that the movement of CSF in the ventricles and around the brain in vivo may mechanically drive rhythmogenesis in the developing CNS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Central Nervous System / drug effects
  • Central Nervous System / embryology
  • Central Nervous System / growth & development
  • Central Nervous System / physiology*
  • Cerebrospinal Fluid / metabolism*
  • Electric Stimulation / methods
  • Embryo, Mammalian
  • Hydrogen-Ion Concentration
  • In Vitro Techniques
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology*
  • Mice
  • Models, Neurological
  • Motor Neurons / physiology*
  • Nerve Net / drug effects
  • Nerve Net / physiology*
  • Oxygen / metabolism
  • Periodicity*
  • Potassium / pharmacology
  • Statistics, Nonparametric

Substances

  • Potassium
  • Oxygen