Behavioral tests of hippocampal function: simple paradigms complex problems

Behavioral tests have become important tools for the analysis of functional effects of induced mutations in transgenic mice. However, depending on the type of mutation and several experimental parameters. false positive or ne gative findings may be obtained. Given the fact that molecular neurobiologi sts now make increasing use of behavioral paradigms in their research, it i s imperative to revisit such problems. In this review three tests. T-maze s pontaneous alternation task (T-CAT), Context dependent fear conditioning (C DFC). and Morris water maze (MWM) sensitive to hippocampal function, serve as illustrative examples for the potential problems. Spontaneous alternatio n tests are sometimes flawed because the handling procedure makes the test dependent on fear rather than exploratory behavior leading to altered alter nation rates independent of hippocampal function. CDFC can provide misleadi ng results because the context test, assumed to be a configural task depend ent on the hippocampus. may have a significant elemental, i.e. cued. compon ent. MWM may pose problems if its visible platform task is disproportionate ly easier for the subjects to solve than the hidden platform task. if the o rder of administration of visible and hidden platform tasks is not counterb alanced, or if inappropriate parameters are measured, Without attempting to be exhaustive, this review discusses such experimental problems and gives examples on how to avoid them. (C) 2001 Elsevier Science B.V. All rights re served.