Memory Erasure Experiments Indicate a Critical Role of CaMKII in Memory Storage

Neuron. 2017 Sep 27;96(1):207-216.e2. doi: 10.1016/j.neuron.2017.09.010.

Abstract

The abundant synaptic protein CaMKII is necessary for long-term potentiation (LTP) and memory. However, whether CaMKII is required only during initial processes or whether it also mediates memory storage remains unclear. The most direct test of a storage role is the erasure test. In this test, a putative memory molecule is inhibited after learning. The key prediction is that this should produce persistent memory erasure even after the inhibitory agent is removed. We conducted this test using transient viral (HSV) expression of dominant-negative CaMKII-alpha (K42M) in the hippocampus. This produced persistent erasure of conditioned place avoidance. As an additional test, we found that expression of activated CaMKII (T286D/T305A/T306A) impaired place avoidance, a result not expected if a process other than CaMKII stores memory. Our behavioral results, taken together with prior experiments on LTP, strongly support a critical role of CaMKII in LTP maintenance and memory storage.

Keywords: CaMKII-K42M; LTP; conditioned place avoidance; herpes simplex virus; hippocampus.

MeSH terms

  • Animals
  • Avoidance Learning / physiology
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / biosynthesis
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / physiology*
  • Conditioning, Psychological / physiology
  • Hippocampus / physiology*
  • Male
  • Memory / physiology*
  • Phosphorylation
  • Rats

Substances

  • Calcium-Calmodulin-Dependent Protein Kinase Type 2