CONTEXTUAL LEARNING AND CUE ASSOCIATION IN FEAR CONDITIONING IN MICE - A STRAIN COMPARISON AND A LESION STUDY

Fear conditioning with electric shock (unconditioned stimulus, US) pai red with tone cue (conditioned stimulus, CS) has been extensively appl ied in recent molecular neurobiological analysis of hippocampal dysfun ction in mice because the context-dependent test phase of this learnin g paradigm is claimed to detect hippocampal impairment in a specific m anner, whereas the cue-dependent lest serves as a control situation in dependent of hippocampal function. These claims are based on hippocamp al lesion studies performed with rats and have not been conclusively c onfirmed with mice with specific hippocampal lesion. Therefore, I inve stigated how hippocampal ibotenic acid lesion affects conditioned fear in mice. I confirm that extensive lesions localized to the hippocampu s impair context-dependent learning but also show that, unlike in the original rat studies, the behavioral impairment is only partial. Furth ermore, studying two inbred strains of mice (C57BL/6 and DBA/2) with h ighly different hippocampal function, I show that the presence or abse nce of CS during training may influence the mouse's ability to learn c omplex multiple contextual stimuli in a genotype-dependent manner. I c onclude that performance at the 'context' test may be based on complex configural (hippocampal) learning but it can also be based on a more simple elemental (non-hippocampal) learning thus leading to potentiall y false-negative findings in the analysis of hippocampal dysfunction. (C) 1997 Elsevier Science B.V. All rights reserved.