Long-term potentiation-like facilitation through GABAA receptor blockade in the mouse dentate gyrus in vivo

Neuroreport. 2008 Dec 3;19(18):1809-13. doi: 10.1097/WNR.0b013e328319ab94.

Abstract

We have investigated the characteristics of a long-term potentiation (LTP)-like facilitation in vivo through GABAA receptor blockade in C57BL/6 and Alzheimer-model transgenic mice dentate gyrus. Bicuculline induced the 'LTP-like' facilitation in a dose-dependent manner. MK-801 inhibited the induction but not maintenance of 'LTP-like' facilitation through bicuculline. Tetanic LTP was further enhanced by bicuculline, but the 'LTP-like' facilitation was conversely attenuated by tetanus. In transgenic mice expressing mutant human tau as an Alzheimer-model, the 'LTP-like' facilitation through bicuculline was significantly greater than tetanic LTP. Bicuculline recovered tetanic LTP impaired in these transgenic mice. These results suggest that GABAA receptor blockade plays an important role in learning and memory, providing a clue for the clinical use of GABAA antagonists to improve cognitive disorders.

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / physiopathology*
  • Animals
  • Bicuculline / administration & dosage
  • Bicuculline / pharmacology
  • Dentate Gyrus / drug effects
  • Dentate Gyrus / physiology*
  • Disease Models, Animal
  • Dizocilpine Maleate / administration & dosage
  • Dizocilpine Maleate / pharmacology
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Antagonists / administration & dosage
  • Excitatory Amino Acid Antagonists / pharmacology
  • GABA Antagonists / administration & dosage
  • GABA Antagonists / pharmacology*
  • Humans
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation
  • Neurons / drug effects
  • Neurons / physiology
  • tau Proteins / genetics
  • tau Proteins / physiology

Substances

  • Excitatory Amino Acid Antagonists
  • GABA Antagonists
  • tau Proteins
  • Dizocilpine Maleate
  • Bicuculline