The biochemistry of memory: The 26 year journey of a ‘new and specific hypothesis’

This Special Issue of Neurobiology of Learning and Memory dedicated to Dr. Richard Thompson to celebrate his 80th birthday and his numerous contributions to the field of learning and memory gave us the opportunity to revisit the hypothesis we proposed more than 25 years ago regarding the biochemistry of learning and memory. This review summarizes our early 1980s hypothesis and then describes how it was tested and modified over the years following its introduction. We then discuss the current status of the hypothesis and provide some examples of how it has led to unexpected insights into the memory problems that accompany a broad range of neuropsychiatric disorders.

Research highlights
► We updated the hypothesis that calpain plays a critical role in learning.
► BDNF release results in calpain activation and actin polymerization in spines.
► A fraction of dendritic spines are enlarged with learning in hippocampus.
► Alterations of the actin polymerization cascade underlie many learning disorders.