Brain plasticity: influence of environment.

Abstract

T he following reprinted article is the first of two classic works included in our series that involve an area of great importance to neuropsychiatry: the study of how environment and life experience influence brain structure. The study of brain plasticity is crucial to understanding the biology of learning and memory, as well as the potential of the brain to recover from injury. In this issue we feature a study by Drs. Edward Bennett, Marian Diamond, David Krech, and Mark Rosenzweig of the University of California, Berkeley, which demonstrates that rats living in an enriched environment have an increase in brain weight and thickness of the cortex and an increase in total brain acetylcholinesterase activity compared with littermates living in more restricted settings.’ In a subsequent issue we will reprint one of several landmark studies by David Hubel and Torsten Wiesel, who in the early 1960s demonstrated that the cytoarchitectune of the visual cortex is greatly responsive to manipulations of visual stimulation during early development. Mark Rosenzweig, in a recent historical review of the search for the biological basis of brain plasticity,2 dates the first controlled study of environmental experience and brain structure to the eighteenth century. Michele Malacame (1744-1816), an Italian anatomist, took a pair of dogs from the same litter and several pairs of birds from clutches of eggs and gave one in each pair extensive training over several years. Examination of the brains showed that animals with intensive training had more folds in the cerebellum. Years later, Charles Darwin observed that domesticated animals had smaller brains than their wild counterparts.3 He speculated that this was due in part to a relative impoverishment of life experience brought on by domestication.4 Santiago Ram#{243}n y Cajal, the great Spanish neurohistologist, believed that learning and enriched mental experience increased the number of neuronal branches.5 Donald Hebb, who was a major influence on Dr. Rosenzweig, reported that animals raised in an enriched environment performed better on multiple learned tasks.6 Hubel and Wiesel7 showed that depriving kittens of visual stimulation in one or both eyes results in structural change to the visual cortex. Drs. Rosenzweig, Knech, and Bennett in the mid-1950s became interested in the correlation between problemsolving ability in animals and brain acetylcholinestenase (AChE) activity.8 To their surprise, they found that cortical AchE activity varied as a function of the intensity of training their rats had received.9 Out of practical and economic considerations, they shifted their experimental paradigm from intensive training to a comparison of enriched versus restricted environments. They recruited Dr. Diamond to enhance their anatomic studies. Since they were interested in measuring AchE activity per unit weight of brain mass, they were able to discover something even more remarkable. The animals raised in enriched environments had a small but a reliable increase in brain weight compared with littermates raised in restricted environments.’0 These researchers subsequently pursued many replication and control studies, described in their article reprinted here, that showed that this finding was not an artifact of isolation stress, differential handling, or locomotor activity. In addition, they found that this effect occurred in animals at all points of the life cycle. Their further studies also showed effects of experience on detailed anatomic measures such as numbers of dendritic spines, nerve cell volume, and numbers of glial cells. Dr. Bennett, in a telephone interview, said that at the time of this study few people believed that the brain would respond like a muscle with usage. And Dr. Rosenzweig affirmed that “training can modulate the genetic given.” Many other groups have replicated their findings, including Volkmar and Greenough at the University of Illinois, Champaign, who demonstrated that animals raised in enriched environments have greater dendritic branching in the occipital cortex.” Currently, the study of macroscopic and molecular structural changes associated with experience, learning, and memory is a large and fascinating area of