In both humans and animals, the hippocampus is critical to memory across modalities of information (e.g., spatial and nonspatial memory) and plays a critical role in the organization and flexible expression of memories. Recent studies have advanced our understanding of cellular basis of hippocampal function, showing that N-methyl-d-aspartate (NMDA) receptors in area CA1 are required in both the spatial and nonspatial domains of learning. Here we examined whether CA1 NMDA receptors are specifically required for the acquisition and flexible expression of nonspatial memory. Mice lacking CA1 NMDA receptors were impaired in solving a transverse patterning problem that required the simultaneous acquisition of three overlapping odor discriminations, and their impairment was related to an abnormal strategy by which they failed to adequately sample and compare the critical odor stimuli. By contrast, they performed normally, and used normal stimulus sampling strategies, in the concurrent learning of three nonoverlapping concurrent odor discriminations. These results suggest that CA1 NMDA receptors play a crucial role in the encoding and flexible expression of stimulus relations in nonspatial memory.

Lhx5 is a member of the LIM homeobox gene family that regulates development of the nervous system. Adult mice generated with a mutation in Lhx5 were found to display absent or disorganized hippocampal neuroanatomy. The pyramidal cell layer in Ammon's horn and the granule cell layer in the dentate gyrus were absent or poorly defined in the hippocampus of adult Lhx5 knockout mice. Behavioral phenotyping of Lhx5 null mutants detected deficits on learning and memory tasks, including the Barnes maze spatial learning task, spontaneous alternation recognition memory, and contextual and cued fear conditioning. General health, neurological reflexes, and sensory abilities appeared to be normal in Lhx5 knockout mice. Motor tests showed impaired performance on some measures of motor activity, coordination, balance, and gait. These results reveal functional outcomes of Lhx5 gene deletion on the integrity of hippocampal neuroanatomy and behavior in the adult mouse.

BACKGROUND AND PURPOSE:Ivermectin is a common anthelmintic drug, widely used in laboratory rodents for treatment of pinworm and mite infestations. We evaluated the action of ivermectin on sensitive behavioral tasks in mice during treatment for mites within a barrier facility.METHODS:A total of 21 (5 males, 16 females) mice (129/SvEv) were used for measuring body weight, open field locomotor activity, and rotarod motor coordination. For acoustic startle and prepulse inhibition, 20 C57BL/6J and 29 AKR/J mice were studied. For the Morris water task, the same 20 C57BL/6J mice were studied. Ivermectin (0.08% sheep drench) was administered in the drinking water of the home cage for 8 weeks. Control groups received normal tap water in identical bottles.RESULTS:Ivermectin did not affect general health, body weight, motor coordination, swimming behavior, or spatial learning in several inbred strains of mice. However, it induced a small but significant effect on some sensitive behaviors.CONCLUSIONS:A cautious approach to initiating ivermectin treatment in mice should be used for sensitive behavioral experiments.

This experiment examined behavior and neurochemistry in adult mice (Mus musculus) after neonatal depletion of monoaminergic fibers projecting to the neocortex and hippocampus. Lesions were made on Postnatal Day 1; mice developed to adulthood and were assessed on simple odor discrimination (SOD) and odor delayed nonmatch-to-sample (DNMS) tasks, passive avoidance (PA), and locomotor activity. On SOD, lesioned mice performed faster than controls but with similar accuracy. On the DNMS task, the lesioned mice performed faster and more accurately than controls. On PA, the lesioned mice exhibited a retention deficit relative to controls. Locomotor activity was similar in the 2 groups. Postmortem analyses revealed that the lesions reduced significantly norepinephrine and serotonin levels in both the neocortex and hippocampus. The data suggest that cortically projecting monoaminergic fibers play an important role in normal cognitive development.

CCAAT/enhancer binding protein delta (C/EBP delta) is a transcriptional regulator implicated in the hepatic acute phase response and in adipogenic and myeloid cell differentiation. We found that C/EBP delta is widely expressed in the peripheral and central nervous systems, including neurons of the hippocampal formation, indicating a role in neural functions. To examine the role of C/EBP delta in vivo, we generated mice with a targeted deletion of the C/EBP delta gene. This mutation does not interfere with normal embryonic and postnatal development. Performance in a battery of behavioral tests indicates that basic neurological functions are normal. Furthermore, performance in a Morris water maze task suggests that C/EBP delta mutant mice have normal spatial learning. However, in the contextual and auditory-cue-conditioned fear task, C/EBP delta null mice displayed significantly more conditioned freezing 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 type of learning and memory.