CURRENT DIRECTIONS IN PSYCHOLOGICAL SCIENCE must be some corresponding change Brain Plasticity and Behavior in the functions mediated by those Bryan Kolb,1 Robbin Gibb, and Terry E. Robinson networks. For the investigator inter- ested in understanding the factors Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, that can change brain circuits, and Alberta, Canada (B.K., RG.), and Department of Psychology, University of Michigan, Ann Arbor, Michigan (T.E.R.) ultimately behavior, a major chal- lenge is to find and to quantify the changes. In principle, plastic changes in neuronal circuits are likely to re- ganisms, such as the tiny worm C. Abstract flect either modifications of exist- elegans, whose nervous system has Although the brain was once ing circuits or the generation of only 302 cells. When the nervous seen as a rather static organ, it is new circuits. But how can research- system changes, there is often a now clear that the organization ers measure changes in neural cir- correlated change in behavior or of brain circuitry is constantly cuitry? Because neural networks psychological function. This behav- changing as a function of expe- are composed of individual neu- ioral change is known by names rience. These changes are re- rons, each of which connects with a such as learning, memory, addiction, ferred to as brain plasticity, subset of other neurons to form in- maturation, and recovery. Thus, for and they are associated with terconnected networks, the logical example, when people learn new functional changes that include place to look for plastic changes is motor skills, such as in playing a phenomena such as memory, at the junctions between neurons, musical instrument, there are plas- addiction, and recovery of that is, at synapses. However, it is a tic changes in the structure of cells function. Recent research has daunting task to determine if syn- in the nervous system that underlie shown that brain plasticity and apses have been added or lost in a the motor skills. If the plastic behavior can be influenced by particular region, given that the changes are somehow prevented a myriad of factors, including human brain has something like from occurring, the motor learning both pre- and postnatal experi- 100 billion neurons and each neuron does not occur. Although psychol- ence, drugs, hormones, matu- makes on average several thousand ogists have assumed that the ner- ration, aging, diet, disease, and synapses. It is clearly impractical to vous system is especially sensitive stress. Understanding how scan the brain looking for altered to experience during develop- these factors influence brain synapses, so a small subset must be ment, it is only recently that they organization and function is identified and examined in detail. have begun to appreciate the po- important not only for under- But which synapses should be tential for plastic changes in the standing both normal and ab- studied? Given that neuroscientists adult brain. Understanding brain normal behavior, but also for have a pretty good idea of what re- plasticity is obviously of consider- designing treatments for be- gions of the brain are involved in able interest both because it pro- havioral and psychological dis- particular behaviors, they can nar- vides a window to understanding orders ranging from addiction row their search to the likely areas, the development of the brain and to stroke. but are still left with an extraordi- behavior and because it allows in- narily complex system to examine. sight into the causes of normal and Keywords There is, however, a procedure that abnormal behavior. addiction; recovery; experi- makes the job easier. ence; brain plasticity In the late 1800s, Camillo Golgi invented a technique for staining a random subset of neurons (1–5%) One of the most intriguing ques- THE NATURE OF BRAIN so that the cell bodies and the den- tions in behavioral neuroscience PLASTICITY dritic trees of individual cells can concerns the manner in which the be visualized (Fig. 1). The den- nervous system can modify its or- The underlying assumption of drites of a cell function as the scaf- ganization and ultimately its func- studies of brain and behavioral plas- folding for synapses, much as tree tion throughout an individual’s ticity is that if behavior changes, branches provide a location for lifetime, a property that is often re- there must be some change in orga- leaves to grow and be exposed to ferred to as plasticity. The capacity nization or properties of the neural sunlight. The usefulness of Golgi’s to change is a fundamental charac- circuitry that produces the behav- technique can be understood by teristic of nervous systems and can ior. Conversely, if neural networks pursuing this arboreal metaphor. be seen in even the simplest of or- are changed by experience, there There are a number of ways one Copyright © 2003 American Psychological Society 1 2 VOLUME 12, NUMBER 1, FEBRUARY 2003 ments were perceived as extreme and thus not characteristic of events experienced by the normal brain. It has become clear, how- ever, not only that synaptic organi- zation is changed by experience, but also that the scope of factors that can do this is much more ex- tensive than anyone had antici- pated. Factors that are now known to affect neuronal structure and be- havior include the following: • experience (both leading pre- and post-natal) • psychoactive drugs (e.g., amphet- amine, morphine) • gonadal hormones (e.g., estrogen, testosterone) • anti-inflammatory agents (e.g., COX-2 inhibitors) • growth factors (e.g., nerve growth factor) • dietary factors (e.g., vitamin and mineral supplements) • genetic factors (e.g., strain differ- ences, genetically modified mice) • disease (e.g., Parkinson’s disease, schizophrenia, epilepsy, stroke) Fig. 1. Photograph of a neuron. In the view on the left, the dendritic field with the • stress extensive dendritic network is visible. On the right are higher-power views of den- • brain injury and leading disease dritic branches showing the spines, where most synapses are located. If there is an increase in dendritic length, spine density, or both, there are presumed to be more synapses in the neuron. We discuss two examples to illus- trate. could estimate how many leaves are Early Experience on a tree without counting every leaf. FACTORS AFFECTING BRAIN Thus, one could measure the total PLASTICITY It is generally assumed that ex- length of the tree’s branches as well periences early in life have differ- as the density of the leaves on a By using Golgi-staining proce- ent effects on behavior than similar representative branch. Then, by sim- dures, various investigators have experiences later in life. The reason ply multiplying branch length by shown that housing animals in for this difference is not under- leaf density, one could estimate to- complex versus simple environ- stood, however. To investigate this tal leafage. A similar procedure is ments produces widespread differ- question, we placed animals in used to estimate synapse number. ences in the number of synapses in complex environments either as ju- About 95% of a cell’s synapses are specific brain regions. In general, veniles, in adulthood, or in senes- on its dendrites (the neuron’s such experiments show that partic- cence (Kolb, Gibb, & Gorny, 2003). branches). Furthermore, there is a ular experiences embellish cir- It was our expectation that there roughly linear relationship be- cuitry, whereas the absence of would be quantitative differences in tween the space available for syn- those experiences fails to do so the effects of experience on synaptic apses (dendritic surface) and the (e.g., Greenough & Chang, 1989). organization, but to our surprise, we number of synapses, so researchers Until recently, the impact of these also found qualitative differences. can presume that increases or de- neuropsychological experiments Thus, like many investigators be- creases in dendritic surface reflect was surprisingly limited, in part fore us, we found that the length of changes in synaptic organization. because the environmental treat- dendrites and the density of syn- Published by Blackwell Publishing Inc. CURRENT DIRECTIONS IN PSYCHOLOGICAL SCIENCE 3 apses were increased in neurons in ments. We were not surprised to ganization. The parallels between the motor and sensory cortical re- find that postinjury experience, drug-induced sensitization and gions in adult and aged animals such as tactile stroking, could mod- memory led us to ask whether the housed in a complex environment ify both brain plasticity and behav- neurons of animals sensitized to (relative to a standard lab cage). In ior because we had come to believe drugs of abuse exhibit long-lasting contrast, animals placed in the that such experiences were power- changes similar to those associated same environment as juveniles ful modulators of brain develop- with memory (e.g., Robinson & showed an increase in dendritic ment (Kolb, Gibb, & Gorny, 2000). Kolb, 1999). A comparison of the ef- length but a decrease in spine den- What was surprising, however, fects of amphetamine and saline sity. In other words, the same envi- was that prenatal experience, such treatments on the structure of neu- ronmental manipulation had quali- as housing the pregnant mother in rons showed that neurons in am- tatively different effects on the a complex environment, could af- phetamine-treated brains had greater organization of neuronal circuitry fect how the brain responded to an dendritic material, as well as more in juveniles than in adults. injury that it would not receive un- densely organized spines. These To pursue this finding, we later til after birth. In other words, pre- plastic changes were not found gave infant animals 45 min of daily natal experience altered the brain’s throughout the brain, however, but tactile stimulation with a little response to injury later in life.