Proper Layering Is Important for Precisely Timed Activation of Hippocampal Mossy Cells

Cereb Cortex. 2010 Sep;20(9):2043-54. doi: 10.1093/cercor/bhp267. Epub 2010 Jan 6.

Abstract

The mammalian cortex exhibits a laminated structure that may underlie optimal synaptic connectivity and support temporally precise activation of neurons. In 'reeler' mice, the lack of the extracellular matrix protein Reelin leads to abnormal positioning of cortical neurons and disrupted layering. To address how these structural changes impact neuronal function, we combined electrophysiological and neuroanatomical techniques to investigate the synaptic activation of hippocampal mossy cells (MCs), the cell type that integrates the output of dentate gyrus granule cells (GCs). While somatodendritic domains of wild-type (WT) MCs were confined to the hilus, the somata and dendrites of reeler MCs were often found in the molecular layer, where the perforant path (PP) terminates. Most reeler MCs received aberrant monosynaptic excitatory input from the PP, whereas the disynaptic input to MCs via GCs was decreased and inhibition was increased. In contrast to the uniform disynaptic discharge of WT MCs, many reeler cells discharged with short, monosynaptic latencies, while others fired with long latencies over a broad temporal window in response to PP activation. Thus, disturbed lamination results in aberrant synaptic connectivity and altered timing of action potential generation. These results highlight the importance of a layered cortical structure for information processing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / genetics
  • Animals
  • Body Patterning / genetics
  • Cell Adhesion Molecules, Neuronal / deficiency
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / physiology*
  • Extracellular Matrix Proteins / deficiency
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / physiology*
  • Mice
  • Mice, Inbred Strains
  • Mice, Neurologic Mutants
  • Mossy Fibers, Hippocampal / abnormalities
  • Mossy Fibers, Hippocampal / metabolism*
  • Mossy Fibers, Hippocampal / pathology
  • Nerve Tissue Proteins / deficiency
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Neurogenesis / genetics
  • Neurons / cytology
  • Neurons / metabolism*
  • Neurons / pathology
  • Serine Endopeptidases / deficiency
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / physiology*
  • Synaptic Transmission / genetics

Substances

  • Cell Adhesion Molecules, Neuronal
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • Serine Endopeptidases
  • reelin protein