VTA DA neuron excitatory synapses in Shank3 Δex4-9 mouse line

Synapse. 2017 Jun;71(6). doi: 10.1002/syn.21955. Epub 2017 Jan 27.

Abstract

Several mutations within SHANK3 gene have been identified in Autism Spectrum Disorder patients and several studies have now started to show that those mutations could impact different brain circuits leading to the heterogeneity of the disease. Here we show that, compared to a mouse model lacking SHANK3 proline-rich containing isoforms, in a mouse model lacking SHANK3 ANK(yrin)-domain containing isoforms, the excitatory synaptic transmission within the Ventral Tegmental Area is not affected. We discuss about the possibility that different domains of SHANK3 are involved in regulating the synapses in a circuit-specific manner resulting in different behavioral and synaptic phenotypes.

Keywords: Autism; Dopamine; SHANK3; Ventral Tegmental Area.

MeSH terms

  • Animals
  • Autism Spectrum Disorder / genetics*
  • Autism Spectrum Disorder / physiopathology
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / physiology*
  • Excitatory Postsynaptic Potentials*
  • Gene Deletion
  • Mice
  • Microfilament Proteins
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Phenotype
  • Protein Domains
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Receptors, AMPA / chemistry
  • Receptors, AMPA / genetics
  • Receptors, AMPA / metabolism
  • Receptors, N-Methyl-D-Aspartate / chemistry
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Ventral Tegmental Area / cytology
  • Ventral Tegmental Area / metabolism
  • Ventral Tegmental Area / physiology*

Substances

  • Microfilament Proteins
  • Nerve Tissue Proteins
  • Protein Isoforms
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • Shank3 protein, mouse