Immunodepression reduces learning performance in male laboratory mice (Mus musculus).

Several theoretical and empirical studies have suggested that immunocompetence may act as a constraint on learning, due to a trade-off in investment in the two processes. Here we tested whether experimentally depressing immune responsiveness of male BKW mice using antithymocyte serum (ATS) would lead to reduced learning performance in a radial maze task. Correct choices in the maze were indicated by the presence of familiar odours, incorrect choices by unfamiliar odours. We showed that temporarily depressing cellular immunity led to a reduction in performance in terms of a reduced proportion of correct choices. We also found a positive relationship between the proportion of correct entries over the period of testing and haemagglutination titre, indicating that mice showing greater immune responsiveness performed better in the maze. We conclude that depressing the immune system reduces learning performance in a combined odour/spatial learning task, and that some individuals are better able to compensate for the experimental immunodepression. In contrast to previous studies, there was no evidence that the effect of ATS was mediated by associated changes in corticosterone or testosterone secretion. There were no significant effects of the presence of female odour on learning performance, and therefore no evidence that the down regulation of learning in relation to immune depression was influenced by apparent reproductive opportunity.

Odour learning and immunity costs in mice.

There is accumulating evidence that learning is metabolically costly. One way in which this may manifest itself is in trade-offs between learning effort and immune function, with learning increasing susceptibility to infection. We tested this idea in the context of odour learning using outbred (BKW) male laboratory mice. Mice were exposed to three experimental treatments in which they were required to learn different numbers of urinary odours. While treatment affected the extent to which mice habituated to test odours during training, differences were not a simple function of the number of odours. The fact that there was also no significant effect of treatment on the degree of preference for novel over familiar odours in subsequent tests suggests mice retained learned odour profiles equally well regardless of the number of odours. That subsequent infection with Babesia microti increased with the number of odours mice had to learn is then consistent with an increased cost to learning effort when more odours were presented. Analysis within treatments, and relationships with the change in corticosterone concentration over the period of the experiment, suggested that it was a failure to learn, rather than maintaining learning performance, in more difficult learning tasks that led to greater infection. As in a previous study of maze learning in the strain, there was no direct relationship between infection and measures of peripheral antibody (total IgG) titre. The results are discussed in relation to studies in other learning contexts and reported relationships between glucocorticoid hormones and learning outcomes.

Adenosine-amino acid interactions in the chick brain: a role in passive avoidance learning.

The present work describes interactions between adenosine and the amino acids glutamate and GABA in slices of intermediate medial hyperstriatum ventrale (IMHV), an area of the chick brain known to be involved in learning and memory events associated with a one-trial passive avoidance task. In slices derived from the IMHV of untrained chicks, the A(1) receptor agonist N(6)-cyclohexyladenosine (CHA; 10 microM) specifically inhibited glutamate release. Conversely, cyclopentyltheophylline (CPT; 100 microM an A(1) antagonist) increased glutamate release from the slices and blocked the CHA-induced inhibition of glutamate. The A(2) receptor agonist 2-p-(2-carboxylethyl)-phenylamino-5'-N-ethylcarboxamido adenosine hydrochloride (CGS 21680) selectively increased glutamate release when applied at 5 microM while it selectively inhibited GABA release at a lower concentration (10 nM). The addition of NMDA to the medium, resulted in increased adenosine release equivalent to that found following stimulation with 50 mM KCl. Both the NMDA and the KCl-induced increases were eliminated by addition of D-2-amino-5 phosphopentanoic acid (D-AP5), an NMDA-receptor antagonist. Slices prepared from the IMHV of chicks following successful training on the task showed enhanced adenosine release 30 min, 1, 3 and 6.5 h after training compared to chicks trained to peck a water-coated bead. The results show that changes in adenosine release from the IMHV accompany memory formation in the chick. We suggest that adenosine-amino acid transmitter interactions potentially via the activation of NMDA receptors, a necessary step in long-term memory formation for the task, may modulate the formation of memory for the one-trial passive avoidance task.

Piracetam facilitates long-term memory for a passive avoidance task in chicks through a mechanism that requires a brain corticosteroid action.

We investigated the effects of piracetam, a nootropic, on learning and memory formation for a passive avoidance task in day-old chicks. To test for the possible cognitive-enhancing properties of piracetam, a weak learning version of this task--whereby chicks maintain a memory to avoid pecking at a bead coated in a diluted aversant for up to 10 h--was used. Post-training (5, 30 or 60 min), but not pretraining, injections of piracetam (10 or 50 mg/kg, i.p.) increased recall for the task when the chicks were tested 24 h later. Because previous studies showed that long-term memory for the passive avoidance task is dependent upon a brain corticosteroid action, and because the efficacy of piracetam-like compounds is also modulated by corticosteroids, we tested whether the facilitating effect of piracetam was dependent upon a corticosteroid action through specific brain receptors (mineralocorticoid receptor and glucocorticoid receptor). First, increased plasma levels of corticosterone were found 5 min after piracetam injection. In addition, intracerebral administration of antagonists for each receptor type (RU28318, for mineralocorticoid receptors, and RU38486 for glucocorticoid receptors; i.c.) given before the nootropic inhibited the facilitative effect of piracetam on memory consolidation. These results give further support to a modulatory action of piracetam on the mechanisms involved in long-term memory formation through a neural action that, in this learning model, requires the activation of the two types of intracellular corticosteroid receptors.

Passive avoidance training and recall are associated with increased glutamate levels in the intermediate medial hyperstriatum ventrale of the day-old chick.

In the young chick, the intermediate medial hyperstriatum ventrale is involved in learning paradigms, including imprinting and passive avoidance learning. Biochemical changes in the intermediate medial hyperstriatum ventrale following learning include an up-regulation of amino-acid transmitter levels and receptor activity. To follow the changes of extracellular amino acid levels during passive avoidance training, we used an in vivo microdialysis technique. Probes were implanted in chicks before training the animals, either on a methylanthranylate- or water-coated bead. One hour later, recall was tested in both groups by presenting a similar bead. An increase of extracellular glutamate levels accompanied training and testing in both groups; during training, glutamate release was higher in methylanthranylate-trained than in water-trained chicks. When compared with the methylanthranylate-trained chicks during testing, the water-trained chicks showed enhanced extra-cellular glutamate levels. No other amino acid examined showed significant changes. After testing, the chicks were anesthetized and release-stimulated with an infusion of 50 mM potassium. Extracellular glutamate and taurine levels were significantly increased in both methylanthranylate- and water-trained chicks. The presentation of methylanthranylate as an olfactory stimulus significantly enhanced glutamate levels, especially in methylanthranylate-trained chicks. The results suggest that such changes in extracellular glutamate levels in the intermediate medial hyperstriatum ventrale accompany pecking at either the water- or the methylanthranylate-bead. The taste of the aversant may be responsible for the greater increases found in methylanthranylate-trained birds.