Lesion Techniques for Behavioral Experiments

Overview

Historically, the lesion method has been one of the most popular techniques used for the study of brain-behavior relationships. The basic theory of lesioning is conceptually very simple: The function of a brain area is inferred by observing the deficits that are produced when the area is removed from the brain. This method of establishing brain-behavior relationships has been used in humans; damage to a brain area through injury or degenerative disease, although not intentionally placed, can still be used to assess brain function. Indeed, much of the very early neurological literature was established by observing the behavioral performance of brain damaged individuals (e.g., Broca, 1861; Hughlings-Jackson, 1931).

Brain lesions have commonly been used to study brain-behavior relationships in animal models as well. In these experiments, researchers attempt to place lesions in restricted brain regions using a variety of techniques and then infer function of the brain areas by observing changes in behavior. This has been a powerful technique for initially establishing the involvement of a brain structure or region in behavior. However, this technique is not without its share of interpretative problems.

First, a lesion effect suggests that the area is involved in the behavior under observation, but does not prove that the brain area is the originating source for brain activity associated with that behavior. For example, if we lesion the abducens nucleus of a rat or rabbit after it has undergone classical eyeblink conditioning, we will see a loss of the eyeblink conditioned response. Does this mean that the critical cellular plasticity responsible for generating the learned response resides in the abducens nucleus? The answer is no; the lesion effect only shows that the structure is located somewhere in the neural circuitry that is responsible for CR generation and performance. In fact, in our example we know that the abducens nucleus contains motoneurons that control musculature that are involved in generating the response and that it is not a site of critical plasticity associated with the learning and memory of the response.

Second, even when a positive lesion effect is noted, depending on the lesion method used, there is a chance that the brain structure or area is not even involved in the behavior under observation. Every brain scientist knows that the brain is made up of clusters of neuronal cell bodies and axons from those cell bodies that course in bundles around the brain. Some lesion methods indiscriminantly destroy cell bodies and axons, thus a researcher cannot be certain if the lesion is affecting cell bodies or axons that are coursing in or near the cell bodies. A lesion that affects the fibers en passant in essence cuts off communication between two areas of the brain. Hence, the observed change in behavior could be due to this loss of connectivity and not due to loss of cell bodies in a given brain area.

Over the years, some improvements in the lesion technique have addressed the two problems outlined above. First, many researchers have coupled neural recording techniques with lesions to further define the involvement of a given brain area in a behavioral function. For example, recording in structures afferent and efferent to the brain area of interest might reveal whether or not the brain area is acting as something more than a passive conduit for critical activity arising elsewhere in the brain. Second, newer chemical lesion techniques have eliminated the problem of lesioning fibers en passant and still newer reversible lesion (or inactivation) methods have allowed well contolled lesions to be temporarily placed while behavioral function is assessed.

In this chapter, we review the nuts and bolts of the lesion technique. We cover the permanent lesion techniques that include aspiration, electrolytic, and chemical lesions as well as temporary inactivation methods (cooling probe and chemical). We believe that while none of these lesion techniques can provide all of the data necessary to evaluate the function of a brain structure or system, all of these lesion techniques can be successfully used to further advance our understanding of brain-behavior relationships.