Brief theta-burst stimulation induces a transcription-dependent late phase of LTP requiring cAMP in area CA1 of the mouse hippocampus

Learn Mem. 1997 Jul-Aug;4(2):230-43. doi: 10.1101/lm.4.2.230.

Abstract

Memory storage in the mammalian brain can be divided into a short-term phase that is independent of new protein synthesis and a long-term phase that requires synthesis of new RNA and proteins. A cellular model for these two phases has emerged from studies of long-term potentiation (LTP) in the three major excitatory synaptic pathways in the hippocampus. One especially effective protocol for inducing robust and persistent LTP is "theta-burst" stimulation, which is designed to mimic the firing patterns of hippocampal neurons recorded during exploratory behavior in intact awake animals. Unlike LTP induced by non-theta tetanization regimens, little is known about the biochemical mechanisms underlying theta-burst LTP in the hippocampus. In the present study, we examined theta-burst LTP in the Schaffer collateral pathway. We found that 3 sec of theta-burst stimulation induced a robust and persistent potentiation (theta L-LTP) in mouse hippocampal slices. This theta L-LTP was dependent on NMDA receptor activation. The initial or early phase of theta-LTP did not require either protein or RNA synthesis and was independent of cAMP-dependent protein kinase (PKA) activation. In contrast, the late phase of theta-LTP required synthesis of proteins and RNA and was blocked by inhibitors of PKA. Prior induction of theta-LTP also occluded the potentiation elicited by chemical activation of PKA. Our results show that, like non-theta LTP, theta-induced LTP in area CA1 of the mouse hippocampus also involves transcription, translation, and PKA and suggest that cAMP-mediated gene transcription may be a common mechanism responsible for the late phases of LTP induced by both theta and non-theta patterns of stimulation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cyclic AMP / analogs & derivatives
  • Cyclic AMP / metabolism*
  • Cyclic AMP / pharmacology
  • Electric Stimulation
  • Gene Expression Regulation* / drug effects
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Learning / physiology*
  • Long-Term Potentiation / physiology*
  • Male
  • Memory / physiology
  • Mice
  • Mice, Inbred C57BL
  • Neural Pathways / physiology
  • Neurons / physiology*
  • Protein Biosynthesis
  • Pyramidal Tracts / physiology
  • Theta Rhythm*
  • Thionucleotides / pharmacology
  • Transcription, Genetic* / drug effects

Substances

  • Thionucleotides
  • adenosine-3',5'-cyclic phosphorothioate
  • Cyclic AMP