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Anatomic studies are used to evaluate the nervous system by examining the cellular organization or chemical composition of specific brain regions or by examining how different brain regions are related by afferent or efferent connections. These studies most commonly involve either the use of tracer substances to label and visualize neural pathways or the use of lesion techniques to destroy a discrete area of brain cells and examine the course of degenerating fibers. Electrolytic and radio frequency techniques, as well as those using neurotoxins, can be used to make brain lesions. Stereotaxic approaches are often used to make more focal lesions or lesions in deeper brain structures. When tracers are used, they are injected into the nervous tissue, where they are incorporated into neuronal cell bodies and/or processes and then transported anterograde or retrograde. Transport of tracers and degeneration of fiber pathways generally occur over a period of several days after injection or a lesion; therefore, an animal must be allowed to survive for a short period before being sacrificed for study of its nervous system. The possibility of using labeled substances, such as manganese, in combination with brain imaging to trace anatomic connections is also developing (Saleem et al., 2002); the same animal can be examined repeatedly with this technology, so it reduces the number of animals needed for a particular study (see “Imaging Studies,” below).
Various factors will determine whether and to what extent the IACUC and the investigator need to exercise flexibility in interpreting and implementing the recommendations of the Guide. Those factors include the invasiveness of the