Present concepts of the neural basis of behavior are based on ideas of concerted activity from many brain regions. Therefore, techniques for mapping the functional activity of the whole brain have become increasingly important in recent years. Patterns of inducible transcription factor expression and 2-deoxyglucose utilization can provide rich information about alterations of neural activity during animal behavior and learning. Whilst such studies allow localization of even subtle behavior-induced changes, they have yielded primarily two-dimensional (2-D) results, showing patterns of activity within individual brain sections. Because of the complexity of brain topology, however, it is often impossible to evaluate activity patterns and the spatial relationship between different activated structures from a set of separate brain sections. Therefore, we have developed a computer-based system aimed at 3-D reconstruction of functional brain activity, as revealed by in situ hybridization neuromapping techniques, and its alignment to brain neuroanatomy. This system allows for several types of analysis, including: (1) comparison of functional activity patterns in several different brains or groups of brains; (2) comparison of 3-D brain activity patterns obtained by different mapping techniques; and (3) correlation of variations in animal behavior with activated brain structure patterns.

The software consists of: (1) a module for semi-automatic alignment of consecutive sections, creating a 3-D model from 2-D planes and thereby restoring the original shape and orientation of the brain prior to sectioning; (2) a graphic editor module, creating electronic 3-D brain atlases from standard animal brain histological sections; (3) a module for warping the 3-D reconstruction of mapped experimental data into the geometry of a standard 3-D brain atlas, with corrections for brain size, plane of sectioning, fixation and shrinkage artifacts; (4) a volume visualization module for rotating and viewing mapped data, either in different planar cuts with the 3-D model, or as semi-transparent images using volume-rendering techniques; (5) an image analysis module for quantifying 3-D patterns of brain activity. The entire activated neuronal population can thus be seen in a single image, and measurements made for particular brain areas. Via 3-D reconstructions, brain regions can be viewed from different angles and rotated on the computer screen, allowing insights into the pattern of behavior-activated brain structures, which is difficult to detect in series of individual brain sections.

Paper presented at Measuring Behavior 2002 , 4^th International Conference on Methods and Techniques in Behavioral Research, 27-30 August 2002, Amsterdam, The Netherlands

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