Impaired Hippocampal Synaptic Plasticity and Enhanced Excitatory Transmission in a Novel Animal Model of Autism Spectrum Disorders with Telomerase Reverse Transcriptase Overexpression

Mol Cells. 2018 May 31;41(5):486-494. doi: 10.14348/molcells.2018.0145. Epub 2018 Apr 26.


Recently, we have reported that animals with telomerase reverse transcriptase (TERT) overexpression exhibit reduced social interaction, decreased preference for novel social interaction and poor nest-building behaviors symptoms that mirror those observed in human autism spectrum disorders (ASD). Overexpression of TERT also alters the excitatory/inhibitory (E/I) ratio in the medial prefrontal cortex. However, the effects of TERT overexpression on hippocampal-dependent learning and synaptic efficacy have not been investigated. In the present study, we employed electrophysiological approaches in combination with behavioral analysis to examine hippocampal function of TERT transgenic (TERT-tg) mice and FVB controls. We found that TERT overexpression results in enhanced hippocampal excitation with no changes in inhibition and significantly impairs long-term synaptic plasticity. Interestingly, the expression levels of phosphorylated CREB and phosphory-lated CaMKIIα were significantly decreased while the expression level of CaMKIIα was slightly increased in the hippocampus of TERT-overexpressing mice. Our observations highlight the importance of TERT in normal synaptic function and behavior and provide additional information on a novel animal model of ASD associated with TERT overexpression.

Keywords: ASD; E/I imbalance; TERT; hippocampus; long-term potentiation.

MeSH terms

  • Animals
  • Autism Spectrum Disorder / enzymology
  • Autism Spectrum Disorder / physiopathology*
  • CA1 Region, Hippocampal / enzymology
  • CA1 Region, Hippocampal / physiology
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / biosynthesis
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
  • Cyclic AMP Response Element-Binding Protein / biosynthesis
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Disease Models, Animal*
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Gene Expression
  • Hippocampus / enzymology
  • Inhibitory Postsynaptic Potentials / drug effects
  • Inhibitory Postsynaptic Potentials / physiology
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics
  • Neuronal Plasticity*
  • Neurotoxins / pharmacology
  • Patch-Clamp Techniques
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / enzymology
  • Pyramidal Cells / physiology*
  • Recombinant Proteins / metabolism
  • Synaptic Transmission* / drug effects
  • Telomerase / genetics
  • Telomerase / physiology*
  • Tetrodotoxin / pharmacology


  • Creb1 protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • Nerve Tissue Proteins
  • Neurotoxins
  • Recombinant Proteins
  • Tetrodotoxin
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Telomerase
  • Tert protein, mouse