Long-term potentiation in vivo in the intact mouse hippocampus

Uk Namgung, Eric Valcourt, Aryeh Routtenberg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

We describe the characteristics of long-term potentiation (LTP) in the intact mouse. Perforant path stimulation evokes both a population excitatory postsynaptic potential (pop-EPSP) and a population spike potential (pop-spike) from the hippocampal dentate gyrus in urethane anesthetized animals. LTP, as measured by increased pop-spike amplitude and pop-EPSP slope, was successfully induced and reliably maintained at a stable level for at least 12 h, the longest time tested. The LTP-inducing stimulus (3 trains of 400 Hz, 8 0.4 ms pulses/train) used in two strains of mice was less by half than that used in rat. These parameters for inducing LTP were also successfully applied to obtain LTP in two different transgenic mouse strains: one bearing a F1/GAP-43 promoter-lacZ fusion gene and another which overexpresses the S100β gene. We also examined the effects of protein synthesis inhibitors, cycloheximide (CXM) and anisomycin (ANI). When CXM or ANI was given 30 min before LTP induction, there was no persistent loss of LTP at the 4 h time point. However, if CXM was given 4 h before LTP induction, significant decay of the potentiated responses occurred 90 min after induction. Half of the animals receiving CXM but not ANI showed a complete and sudden elimination of the entire response after the LTP-inducing stimulus. It was speculated that loss of a constitutively-expressed housekeeping protein, for example a calcium buffering protein, with an estimated half-life of 2 h would lead to an inability to buffer LTP-induced alterations, such as intracellular calcium elevation, increasing intracellular calcium to toxic levels. LTP can be reliably studied in the intact mouse hippocampus and can be usefully applied in both wild-type and transgenic preparations. It will afford the opportunity to study LTP in mouse mutants in their in vivo state rather than in vitro in the slice preparation permitting characterization of biochemical and molecular events after LTP and then to determine the explicit relation of these events with the physiology of synaptic enhancement.

Original languageEnglish (US)
Pages (from-to)85-92
Number of pages8
JournalBrain research
Volume689
Issue number1
DOIs
StatePublished - Aug 14 1995

Keywords

  • Anisomycin
  • Calcium buffering
  • Cycloheximide
  • Dentate granule cell
  • Long-term potentiation
  • Mouse
  • Protein synthesis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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