Neurophysiological modification of CA1 pyramidal neurons in a transgenic mouse expressing a truncated form of disrupted-in-schizophrenia 1

Clair A. Booth, Jonathan T. Brown, Andy D Randall

Research output: Contribution to journalArticle (Academic Journal)peer-review

20 Citations (Scopus)

Abstract

A t(1;11) balanced chromosomal translocation transects the Disc1 gene in a large Scottish family and produces genome-wide linkage to schizophrenia and recurrent major depressive disorder. This study describes our in vitro investigations into neurophysiological function in hippocampal area CA1 of a transgenic mouse (DISC1(tr)) that expresses a truncated version of DISC1 designed to reproduce aspects of the genetic situation in the Scottish t(1;11) pedigree. We employed both patch-clamp and extracellular recording methods in vitro to compare intrinsic properties and synaptic function and plasticity between DISC1(tr) animals and wild-type littermates. Patch-clamp analysis of CA1 pyramidal neurons (CA1-PNs) revealed no genotype dependence in multiple subthreshold parameters, including resting potential, input resistance, hyperpolarization-activated 'sag' and resonance properties. Suprathreshold stimuli revealed no alteration to action potential (AP) waveform, although the initial rate of AP production was higher in DISC1(tr) mice. No difference was observed in afterhyperpolarizing potentials following trains of 5-25 APs at 50Hz. Patch-clamp analysis of synaptic responses in the Schaffer collateral commissural (SC) pathway indicated no genotype-dependence of paired pulse facilitation, excitatory postsynaptic potential summation or AMPA/NMDA ratio. Extracellular recordings also revealed an absence of changes to SC synaptic responses and indicated input-output and short-term plasticity were also unaltered in the temporoammonic (TA) input. However, in DISC1(tr) mice theta burst-induced long-term potentiation was enhanced in the SC pathway but completely lost in the TA pathway. These data demonstrate that expressing a truncated form of DISC1 affects intrinsic properties of CA1-PNs and produces pathway-specific effects on long-term synaptic plasticity.

Original languageEnglish
Pages (from-to)1074-1090
Number of pages17
JournalEuropean Journal of Neuroscience
Volume39
Issue number7
DOIs
Publication statusPublished - Apr 2014

Keywords

  • psychiatric disease
  • excitability
  • susceptibility gene
  • synaptic plasticity
  • hippocampus
  • electrophysiology
  • LONG-TERM POTENTIATION
  • SPIKE AFTER-DEPOLARIZATION
  • SYNAPTIC PLASTICITY
  • BURST GENERATION
  • SCHIZOAFFECTIVE DISORDER
  • BEHAVIORAL PHENOTYPES
  • DEPENDENT DEPRESSION
  • BIPOLAR DISORDER
  • MENTAL-ILLNESS
  • DISC1

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