Core Differences in Synaptic Signaling Between Primary Visual and Dorsolateral Prefrontal Cortex

Cereb Cortex. 2018 Apr 1;28(4):1458-1471. doi: 10.1093/cercor/bhx357.

Abstract

Neurons in primary visual cortex (V1) are more resilient than those in dorsolateral prefrontal cortex (dlPFC) in aging, schizophrenia and Alzheimer's disease. The current study compared glutamate and neuromodulatory actions in macaque V1 to those in dlPFC, and found striking regional differences. V1 neuronal firing to visual stimuli depended on AMPA receptors, with subtle NMDA receptor contributions, while dlPFC depends primarily on NMDA receptors. Neuromodulatory actions also differed between regions. In V1, cAMP signaling increased neuronal firing, and the phosphodiesterase PDE4A was positioned to regulate cAMP effects on glutamate release from axons. HCN channels in V1 were classically located on distal dendrites, and enhanced cell firing. These data contrast with dlPFC, where PDE4A and HCN channels are concentrated in thin spines, and cAMP-HCN signaling gates inputs and weakens firing. These regional differences may explain why V1 neurons are more resilient than dlPFC neurons to the challenges of age and disease.

Publication types

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

MeSH terms

  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Animals
  • Cardiovascular Agents / pharmacology
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / metabolism
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / ultrastructure
  • Dendritic Spines / drug effects
  • Dendritic Spines / ultrastructure
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Antagonists / pharmacology
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / metabolism
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / ultrastructure
  • Macaca mulatta
  • Membrane Potentials / drug effects
  • Microscopy, Immunoelectron
  • Nerve Net / drug effects
  • Nerve Net / physiology*
  • Neurons / drug effects
  • Neurons / physiology*
  • Neurons / ultrastructure
  • Photic Stimulation
  • Prefrontal Cortex / cytology*
  • Pyrimidines / pharmacology
  • Signal Transduction / drug effects
  • Synapses / drug effects
  • Synapses / physiology*
  • Synapses / ultrastructure
  • Visual Cortex / cytology*

Substances

  • Cardiovascular Agents
  • Excitatory Amino Acid Antagonists
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Pyrimidines
  • ICI D2788
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • PDE4A protein, human