SELECTIVELY ENHANCED CONTEXTUAL FEAR CONDITIONING IN MICE LACKING THETRANSCRIPTIONAL REGULATOR CCAAT ENHANCER-BINDING-PROTEIN-DELTA/

CCAAT/enhancer binding protein delta (C/EBP delta) is a transcriptiona l regulator implicated in the hepatic acute phase response and in adip ogenic and myeloid cell differentiation. We found that C/EBP delta is widely expressed in the peripheral and central nervous systems, includ ing neurons of the hippocampal formation, indicating a role in neural functions. To examine the role of C/EBP delta in vivo, we generated mi ce with a targeted deletion of the C/EBP delta gene. This mutation doe s not interfere with normal embryonic and postnatal development. Perfo rmance in a battery of behavioral tests indicates that basic neurologi cal functions are normal. Furthermore, performance in a Morris water m aze task suggests that C/EBP delta mutant mice have normal spatial lea rning. However, in the contextual and auditory-cue-conditioned fear ta sk, C/EBP delta null mice displayed significantly more conditioned fre ezing to the test context than did wild-type controls, but equivalent conditioning to the auditory cue, These data demonstrate a selectively enhanced contextual fear response in mice carrying a targeted genomic mutation and implicate C/EBP delta in the regulation of a specific ty pe of learning and memory.