Impaired prepulse inhibition in mice with IRSp53 deletion in modulatory neurotransmitter neurons including dopamine, acetylcholine, oxytocin, and serotonin

Biochem Biophys Res Commun. 2022 Jan 1:586:114-120. doi: 10.1016/j.bbrc.2021.11.049. Epub 2021 Nov 20.

Abstract

Prepulse inhibition (PPI) is a neurophysiological finding that is decreased in schizophrenia patients and has been used in pathophysiology studies of schizophrenia and the development of antipsychotic drugs. PPI is affected by several drugs including amphetamine, ketamine, and nicotinic agents, and it is reported that several brain regions and modulatory neurotransmitters are involved in PPI. Here we showed that mice with IRSp53 deletion in each dopaminergic, cholinergic, oxytocinergic, and serotoninergic modulatory neurons showed a decrease in PPI. Other than PPI, there were no other behavioral changes among IRSp53 deletion mice. Through this study, we could reconfirm that dysfunction of each modulatory neuron such as dopamine, acetylcholine, oxytocin, and serotonin can result in PPI impairment, and it should be considered that PPI could be broadly affected by changes in one of a certain kind of modulatory neurons.

Keywords: Acetylcholine; Dopamine; IRSp53; Oxytocin; Prepulse inhibition; Schizophrenia; Serotonin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism
  • Animals
  • Brain / metabolism*
  • Brain / pathology
  • Brain Mapping
  • Cholinergic Neurons / metabolism*
  • Cholinergic Neurons / pathology
  • Dopamine / metabolism
  • Dopaminergic Neurons / metabolism*
  • Dopaminergic Neurons / pathology
  • Gene Deletion
  • Genes, Reporter
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / deficiency
  • Nerve Tissue Proteins / genetics*
  • Noise
  • Oxytocin / metabolism
  • Prepulse Inhibition*
  • Reflex, Startle
  • Serotonergic Neurons / metabolism*
  • Serotonergic Neurons / pathology
  • Serotonin / metabolism

Substances

  • Baiap2 protein, mouse
  • Nerve Tissue Proteins
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Serotonin
  • Oxytocin
  • Acetylcholine
  • Dopamine