Bidirectional global spontaneous network activity precedes the canonical unidirectional circuit organization in the developing hippocampus

J Comp Neurol. 2014 Jun 15;522(9):2191-208. doi: 10.1002/cne.23528.

Abstract

Spontaneous network activity is believed to sculpt developing neural circuits. Spontaneous giant depolarizing potentials (GDPs) were first identified with single-cell recordings from rat CA3 pyramidal neurons, but here we identify and characterize a large-scale spontaneous network activity we term global network activation (GNA) in the developing mouse hippocampal slices, which is measured macroscopically by fast voltage-sensitive dye imaging. The initiation and propagation of GNA in the mouse is largely GABA-independent and dominated by glutamatergic transmission via AMPA receptors. Despite the fact that signal propagation in the adult hippocampus is strongly unidirectional through the canonical trisynaptic circuit (dentate gyrus [DG] to CA3 to CA1), spontaneous GNA in the developing hippocampus originates in distal CA3 and propagates both forward to CA1 and backward to DG. Photostimulation-evoked GNA also shows prominent backward propagation in the developing hippocampus from CA3 to DG. Mouse GNA is strongly correlated to electrophysiological recordings of highly localized single-cell and local field potential events. Photostimulation mapping of neural circuitry demonstrates that the enhancement of local circuit connections to excitatory pyramidal neurons occurs over the same time course as GNA and reveals the underlying pathways accounting for GNA backward propagation from CA3 to DG. The disappearance of GNA coincides with a transition to the adult-like unidirectional circuit organization at about 2 weeks of age. Taken together, our findings strongly suggest a critical link between GNA activity and maturation of functional circuit connections in the developing hippocampus.

Keywords: development; imaging; photostimulation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / growth & development*
  • Hippocampus / physiology*
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Mice, Inbred C57BL
  • Microelectrodes
  • Neural Pathways / drug effects
  • Neural Pathways / growth & development
  • Neural Pathways / physiology
  • Neurons / drug effects
  • Neurons / physiology
  • Photic Stimulation
  • Pyramidal Cells / cytology
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / growth & development
  • Pyramidal Cells / physiology
  • Receptors, GABA-B / metabolism
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Synapses / drug effects
  • Synapses / physiology
  • Tissue Culture Techniques
  • Voltage-Sensitive Dye Imaging

Substances

  • Receptors, GABA-B
  • Receptors, N-Methyl-D-Aspartate