Paul J. Lombroso, M.D., Marilee P. Ogren, Ph.D. Assistant Editors
Learning and Memory, Part I: Brain Regions Involved in Two Types of Learning and Memory
PAUL J. LOMBROSO, M.D.,
MARILEE P. OGREN, PH.D.
As presented in the previous two columns on fragile X syndrome,1,2 the absence of fragile X mental retardation protein in fragile Xdisrupts the transport of messages (messenger RNAs [mRNAs]) along dendrites and their translation into proteins. This is because one of the functions of fragile X mental retardation protein is to normally repress local translation of mRNAs at sites adjacent to synapses, and in its absence, mRNAs are inappropriately translated. Researchers also found that activating a specific subtype of glutamatereceptor (metabotropic glutamate receptor 5 [mGluR5]) is an important signal that initiates the translation of mRNAs at synapses. These two observations were put together to formulate a new hypothesis, called the BmGluR hypothesis of fragile X syndrome.[ It suggests that reducing mGluR5 signaling might reduce the excessive translation of synaptic proteins in fragile X. One target of therapeuticintervention therefore is to develop mGluR5 antagonists and try these drugs first in animal models of fragile X syndrome and eventually in patient populations. This column and the next take the story further to discuss some of the molecular events that actually occur inside neurons during the development of synaptic plasticity and how these changes in synaptic strength can be measured in the laboratory.Among the topics that we cover are long-term potentiation and some of the mechanisms thought to explain why Bneurons that fire together wire together.[
Accepted July 3, 2008. Dr. Ogren is with Boston College, and Dr. Lombroso is with the Yale University Child Study Center. Correspondence to Marilee Ogren, Ph.D., Biology Department, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467;e-mail: ogren@MIT.edu. 0890-8567/08/4711-1228 Ó2008 by the American Academy of Child and Adolescent Psychiatry DOI: 10.1097/CHI.0b013e318186e638
We begin with a biking accident. Approximately 70 years ago, in a small town outside Hartford, Connecticut, a young boy was riding his bicycle when he fell off and hit his head. Soon thereafter, he developed a seizure disorder. The story of H.M. hasbeen told and retold over the years and is only briefly summarized here. Initially, H.M. was successfully treated with anticonvulsant medications, but his seizures continued to get worse and became profoundly disabling over the next decade. He had difficulties finishing school and maintaining employment. In 1953, when H.M. was 27 years old, in an attempt to control the seizures, a surgicalprocedure was proposed to remove from within the medial temporal lobes what was believed to be sclerotic tissue that had formed after the head trauma. Dr. William Scofield performed bilateral medial temporal lobotomies that removed the hippocampi, the parahippocampal cortex, and parts of the amygdala. After the surgery, H.M.’s seizures were much better controlled. However, it was soon apparent that he hadalso lost the ability to form new declarative memories. These types of memories are those that one is conscious of and can talk about. H.M. is still alive today and has met with the psychologist Dr. Brenda Milner for a hundred times, yet he retains no memory of her and has to be introduced each time they meet. He retains new information for only minutes at a time and has lost the ability to turnthese short-term memories into longlasting memories, a process called consolidation. It is important to realize that H.M. retains and can recall many memories formed before surgery and occasionally retains new information for longer periods but only with excessive practice. These seminal studies by Scoville and Milner3 established the role of the hippocampus in the consolidation of declarative...