Inducible and selective erasure of memories in the mouse brain via chemical-genetic manipulation

Neuron. 2008 Oct 23;60(2):353-66. doi: 10.1016/j.neuron.2008.08.027.

Abstract

Rapid and selective erasures of certain types of memories in the brain would be desirable under certain clinical circumstances. By employing an inducible and reversible chemical-genetic technique, we find that transient alphaCaMKII overexpression at the time of recall impairs the retrieval of both newly formed one-hour object recognition memory and fear memories, as well as 1-month-old fear memories. Systematic analyses suggest that excessive alphaCaMKII activity-induced recall deficits are not caused by disrupting the retrieval access to the stored information but are, rather, due to the active erasure of the stored memories. Further experiments show that the recall-induced erasure of fear memories is highly restricted to the memory being retrieved while leaving other memories intact. Therefore, our study reveals a molecular genetic paradigm through which a given memory, such as new or old fear memory, can be rapidly and specifically erased in a controlled and inducible manner in the brain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / physiology
  • Brain / enzymology*
  • Brain / physiopathology
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics*
  • Cats
  • Conditioning, Psychological / physiology
  • Fear / physiology*
  • Gene Expression Regulation, Enzymologic / genetics
  • Genetic Therapy / methods
  • Memory Disorders / enzymology*
  • Memory Disorders / genetics*
  • Memory Disorders / physiopathology
  • Mice
  • Mice, Transgenic
  • Molecular Biology / methods
  • Recognition, Psychology / physiology*
  • Smell / physiology
  • Stress Disorders, Post-Traumatic / enzymology
  • Stress Disorders, Post-Traumatic / genetics
  • Stress Disorders, Post-Traumatic / therapy
  • Time Factors
  • Up-Regulation / genetics

Substances

  • Calcium-Calmodulin-Dependent Protein Kinase Type 2