Summary

Brain plasticity refers to the potential for the brain to change physically, chemically or physiologically to adapt to environmental change and to compensate for brain perturbations such as injury. Although there is a tendency to perceive plasticity as a singular change in which synapses are added or subtracted, experience-dependent change in the nervous system is much more complex and it is clear that experience modulates plasticity in unpredictable ways. Thus, the same experience can have different effects at different ages, in the two sexes, in the two hemispheres and in different cortical layers and regions. Many of these differential changes present a paradox in that they are not predictable a priori. The challenge is to understand how plastic changes occur, which ultimately will be at the level of gene expression, so that the rules governing brain plasticity can be written.

Introduction

Behavioural neuroscience has been guided throughout the twentieth century by the principle of localization of function. One underlying assumption has been that there are continuously adaptive responses to the experiences that challenge the cerebral cortex – processes referred to as plasticity. For example, if we learn a motor skill such as playing the piano, there are correlated changes in the organization of the motor representations of the fingers in the cerebral cortex. Indeed, it is likely that the increasing dexterity of the fingers as the piano-playing skill improves occurs because of the changed motor representation.

An important development in behavioral neuroscience in the last 20 years has been the demonstration that it is possible to stimulate functional recovery after brain injury in laboratory animals. A significant challenge for the next 20 years is the translation of this work to improve the outcome from brain injury and disease in humans. Rodent models of early brain injury provide a tool for developing such rehabilitation programs. The models include analyses at different levels including detailed behavioral paradigms, electrophysiology, neuronal morphology, protein chemistry, and epigenetics. Our goal here is to synthesize this multidisciplinary work to provide a platform for moving to the clinic.

The road to translation begins with a search for an understanding of brain development and the factors that modify “normal” development. This allows us to outline a series of principles of cerebral plasticity that provide a framework from which to launch a search for rehabilitation treatments for animals with injuries of varying etiologies. By necessity this requires an investigation of behavior, neuronal morphology, neurophysiology, protein chemistry, and genetics/epigenetics. By using this strategy, we have been able to identify a variety of factors that influence functional recovery and brain plasticity, including the demonstration that both pre-natal factors and peripheral stimulation can profoundly influence functional outcome after perinatal brain injury.

Background

Assumptions and hypotheses

The underlying assumption of our experiments is that there are critical periods during development in which the brain is more able to reorganize, and others where it is less able to reorganize, to allow restoration of function after cerebral injury.