NCAM Regulates Inhibition and Excitability in Layer 2/3 Pyramidal Cells of Anterior Cingulate Cortex

Front Neural Circuits. 2017 Mar 23;11:19. doi: 10.3389/fncir.2017.00019. eCollection 2017.

Abstract

The neural cell adhesion molecule (NCAM), has been shown to be an obligate regulator of synaptic stability and pruning during critical periods of cortical maturation. However, the functional consequences of NCAM deletion on the organization of inhibitory circuits in cortex are not known. In vesicular gamma-amino butyric acid (GABA) transporter (VGAT)-channelrhodopsin2 (ChR2)-enhanced yellow fluorescent protein (EYFP) transgenic mice, NCAM is expressed postnatally at perisomatic synaptic puncta of EYFP-labeled parvalbumin, somatostatin and calretinin-positive interneurons, and in the neuropil in the anterior cingulate cortex (ACC). To investigate how NCAM deletion affects the spatial organization of inhibitory inputs to pyramidal cells, we used laser scanning photostimulation in brain slices of VGAT-ChR2-EYFP transgenic mice crossed to either NCAM-null or wild type (WT) mice. Laser scanning photostimulation revealed that NCAM deletion increased the strength of close-in inhibitory connections to layer 2/3 pyramidal cells of the ACC. In addition, in NCAM-null mice, the intrinsic excitability of pyramidal cells increased, whereas the intrinsic excitability of GABAergic interneurons did not change. The increase in inhibitory tone onto pyramidal cells, and the increased pyramidal cell excitability in NCAM-null mice will alter the delicate coordination of excitation and inhibition (E/I coordination) in the ACC, and may be a factor contributing to circuit dysfunction in diseases such as schizophrenia and bipolar disorder, in which NCAM has been implicated.

Keywords: brain slice; channelrhodopsin; laser scanning photostimulation; mouse; patch clamp.

Publication types

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

MeSH terms

  • Animals
  • Electrophysiological Phenomena / physiology*
  • Gyrus Cinguli / cytology
  • Gyrus Cinguli / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Microscopy, Confocal
  • Neural Cell Adhesion Molecules / physiology*
  • Neural Inhibition / physiology
  • Patch-Clamp Techniques
  • Pyramidal Cells / cytology
  • Pyramidal Cells / physiology*

Substances

  • Neural Cell Adhesion Molecules