Studying the behavior of genetic background strains provides important information for the design and interpretation of cognitive phenotypes in mutant mice. Our experiments examined the performance of three commonly used strains (C57BL/6J, 129S6, DBA/2J) on three behavioral tests for learning and memory that measure very different forms of memory, and for which there is a lack of data on strain differences. In the social transmission of food preference test (STFP) all three strains demonstrated intact memory for an odorcued food that had been sampled on the breath of a cagemate 24 hours previously. While C57BL/6J and 129S6 mice showed good trace fear conditioning, DBA/2J mice showed a profound deficit on trace fear conditioning. In the Barnes maze test for spatial memory, the 129S6 strain showed poor probe trial performance, relative to C57BL/6J mice. Comparison of strains for open field exploratory activity and anxiety-like behavior suggests that poor Barnes maze performance reflects low exploratory behavior, rather than a true spatial memory deficit, in 129S6 mice. This interpretation is supported by good Morris water maze performance in 129S6 mice. These data support the use of a C57BL/6J background for studying memory deficits in mutant mice using any of these tasks, and the use of a 129S6 background in all but the Barnes maze. A DBA/2J background may be particularly useful for investigating the genetic basis of emotional memory using fear conditioning.

Social transmission of food preference (STFP) is a test of olfactory memory that can be used in mice. Confounds in STFP that can lead to misinterpretation of an STFP deficit as a memory impairment include changes in social interaction and olfaction. The issue of changes in social interaction was addressed by evaluating an observer-centric and a demonstrator-centric method for scoring the interaction phase of STFP in mice. The demonstrator-centric method was applied to a line of STFP-impaired, galanin-overexpressing transgenic (GAL-tg). GAL-tg mice were impaired in STFP without deficits in social interaction. In tests of olfactory ability, GAL-tg mice were unimpaired on buried-food and habituation-dishabituation tasks. The current studies describe an expanded method for using STFP in mice and confirm a deficit in olfactory memory in GAL-tg mice.

Galanin inhibits the release of several neurotransmitters and produces performance deficits in a variety of spatial and aversive learning and memory tasks. The experiments in this study investigated the role galanin has in emotional learning and memory using a standard delay cued and contextual fear conditioning task. Rats were administered galanin into the lateral ventricles before training, and scored for freezing behavior in the same context and in a novel context with and without an auditory cue (CS) that had been paired previously with an aversive stimulus (US). Galanin-overexpressing transgenic mice were tested in an identical behavioral protocol. The galanin-administered rats and the transgenic mice were not significantly different from their respective controls on this task. A more challenging trace cued and contextual fear conditioning procedure was administered to separate groups of galanin-treated rats and galanin-overexpressing transgenic mice. Subjects were trained with the same CS and US, however, a 2.5-sec delay was inserted between CS offset and US onset. Following the trace conditioning, rats administered galanin and mice overexpressing galanin both exhibited significantly less freezing to the CS in the novel context as compared with their control groups. These results indicate that the observed disruption of cued fear conditioning was specific to the more difficult trace conditioning task. These findings are the first demonstration that galanin impairs performance on an emotional memory task and support the hypothesis that galanin-induced deficits are specific to more difficult cognitive tasks.Galanin is a neuropeptide expressed in the mammalian brain that inhibits the release of acetylcholine, glutamate, norepinephrine, and serotonin (Bartfai et

The neuropeptide galanin induces performance deficits in a wide range of cognitive tasks in rodents. Three G-protein-coupled galanin receptor subtypes, designated GAL-R1, GAL-R2 and GAL-R3, have been cloned. The present study examined the role of GAL-R1 in cognition by testing mice with a null mutation in Galr1 on several different types of learning and memory tasks. Assessments of general health, neurological reflexes, sensory abilities and motor functions were conducted as control measures. Mutant mice were unimpaired in social transmission of food preference and the Morris water maze. In tests of fear conditioning, mutant mice were unimpaired in a delay version of cued fear conditioning. However, mice homozygous for the null mutation were impaired in a trace version of cued fear conditioning. Mutant mice were unimpaired in contextual fear conditioning, whether training was by the delay or trace protocol. General health, neurological reflexes, sensory abilities and motor functions did not differ across genotypes, indicating that the trace fear conditioning deficit was not an artifact of procedural disabilities. The findings of normal performance on several cognitive tasks and a selective deficit in trace cued fear conditioning in homozygous GAL-R1 mutant mice are discussed in terms of hypothesized roles of the GAL-R1 subtype. The generally normal phenotype of GAL-R1 null mutants supports the use of this line for identification of the receptor subtypes that mediate the cognitive deficits produced by exogenous galanin.

Galanin (GAL) impairs performance on cognitive tasks when administered centrally to rats. GAL transgenic (GAL-tg) mice overexpressing endogenous GAL show deficits on the probe trial of the Morris water maze spatial learning task, on the social transmission of food preference olfactory memory task, and on the trace cued fear conditioning emotional learning and memory task. Knockout mice deficient in the GAL-R1 receptor subtype were normal on most memory tasks, while showing a small deficit in trace cued fear conditioning, suggesting a selective role for the GAL-R1 in aversive memories, and implicating other GAL receptor subtypes in spatial learning and olfactory social memory. The growing body of rodent literature implicating excess GAL in cognitive impairment is relevant to the overexpression of GAL in the basal forebrain during the progression of Alzheimer's disease.