1978 by Mort Mishkin appeared to provide evidence that it was the combined damage to both the hippocampus and the amygdala that led to the most severe memory deficits. Yet, in 1987 when I entered graduate school, Squire and Zola-Morgan at U.C. San Diego were finding evidence that the amygdala might not be involved after all. They had shown in animals that damaging the hippocampus on both sides caused a clear memory deficit, but they found no deficit after damaging just the amygdala on both sides of the brain. Then they did what turned out to be a key experiment. They added very precise damage to the amygdala in animals that had both their hippocampi removed. The researchers saw the addition of the selective amygdala damage did not in fact make the memory deficit worse, as predicted. The question was, If the additional memory impairment was not due to damage to the amygdala, then damage to what brain structure was it due to? A clue to this mystery came from a careful examination of the anatomy of the brain lesions. Neuroanatomist David Amaral was looking at the extent of damage in the brains of these animals in thin sections of tissue and noticed something obvious only to a neuroanatomist: There was a lot more damage than to just the hippocampus and amygdala. Namely, a lot of the cortex surrounding the brain areas of these animals was also damaged, in varying degrees. It was likely that the same damage would be present in patient H.M., given the surgical approach used to make his brain lesion. Maybe the nondescript cortical areas surrounding the hippocampus and amygdala that nobody had ever considered very important, and had previously thought to be part of our visual system, were the key to the mystery.
This is where I entered the picture. Amaral ran a neuroanatomy lab at the Salk Institute in San Diego right across the street from U.C. San Diego, and he was a leading expert on the anatomical organization of the medial temporal lobe. It seemed clear to me that we needed a more careful understanding of the basic structure of this part of the brain, so when they asked me if I wanted to take on that challenge, I jumped at the opportunity. I literally felt like a neuroscientist version of David Livingstone, entering one of the deepest, darkest parts of the brain—somewhere few others had gone before.
I had thought for sure that all parts of the brain had been carefully examined and mapped in 1987 when I entered graduate school, but I soon found out that the areas I was focusing on had fallen through the cracks. I was one of the first to study them carefully. I used some of the same basic techniques that had been used by neuroanatomists since the early 1900s. I examined thin slices of the brain from key temporal lobe areas and stained them with a chemical to show the size and organization of the cell bodies of the neurons and glia that made up the tissue (this technique is called a Nissl stain). I looked at some slices to see if I could identify features that would allow me to differentiate one area from the next. In other studies, I tracked where these areas received inputs from and where they projected to.
I spent hundreds of hours over six years sitting alone in a darkened room staring at brain tissue under a powerful microscope trying to discern a clear pattern. Some days, after hours and hours of looking in the microscope at the cells that made up these brain regions, the images started dancing in front of my eyes like beautiful abstract pieces of art. It was hard, detailed work. Often, to fill the silence, I listened to classical music. Saturday mornings were my favorite microscope days. Sitting in the lab all alone in the dark with my slice of brain tissue I listened to a radio program called Adventures in Good Music with Karl Haas —a wonderful show from which I learned about everything from the mysteries of how Stradivarius made his famous violins to subtleties of the violin passages in Mendelssohn’s symphonies.
This is where I entered the picture. Amaral ran a neuroanatomy lab at the Salk Institute in San Diego right across the street from U.C. San Diego, and he was a leading expert on the anatomical organization of the medial temporal lobe. It seemed clear to me that we needed a more careful understanding of the basic structure of this part of the brain, so when they asked me if I wanted to take on that challenge, I jumped at the opportunity. I literally felt like a neuroscientist version of David Livingstone, entering one of the deepest, darkest parts of the brain—somewhere few others had gone before.
I had thought for sure that all parts of the brain had been carefully examined and mapped in 1987 when I entered graduate school, but I soon found out that the areas I was focusing on had fallen through the cracks. I was one of the first to study them carefully. I used some of the same basic techniques that had been used by neuroanatomists since the early 1900s. I examined thin slices of the brain from key temporal lobe areas and stained them with a chemical to show the size and organization of the cell bodies of the neurons and glia that made up the tissue (this technique is called a Nissl stain). I looked at some slices to see if I could identify features that would allow me to differentiate one area from the next. In other studies, I tracked where these areas received inputs from and where they projected to.
I spent hundreds of hours over six years sitting alone in a darkened room staring at brain tissue under a powerful microscope trying to discern a clear pattern. Some days, after hours and hours of looking in the microscope at the cells that made up these brain regions, the images started dancing in front of my eyes like beautiful abstract pieces of art. It was hard, detailed work. Often, to fill the silence, I listened to classical music. Saturday mornings were my favorite microscope days. Sitting in the lab all alone in the dark with my slice of brain tissue I listened to a radio program called Adventures in Good Music with Karl Haas —a wonderful show from which I learned about everything from the mysteries of how Stradivarius made his famous violins to subtleties of the violin passages in Mendelssohn’s symphonies.
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