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The orbitofrontal cortex.

The orbitofrontal cortex contains the secondary taste cortex, in which the reward value of taste is represented. It also contains the secondary and tertiary olfactory cortical areas, in which information about the identity and also about the reward value of odours is represented. The orbitofrontal cortex also receives information about the sight of objects from the temporal lobe cortical visual areas, and is involved in learning and in reversing stimulus-reinforcement associations. The stimulus might be a visual or olfactory stimulus, and the primary (unlearned) reinforcer a taste or touch. Damage to the orbitofrontal cortex impairs the learning and reversal of stimulus-reinforcement associations, and thus the correction of behavioural responses when these are no longer appropriate because previous reinforcement contingencies change. The information which reaches the orbitofrontal cortex for these functions includes information about faces, and damage to the orbitofrontal cortex can impair face expression identification. This evidence thus shows that the orbitofrontal cortex is involved in decoding some primary reinforcers such as taste; in learning and reversing associations of visual and other stimuli to these primary reinforcers; and plays an executive function in controlling and correcting reward-related and punishment-related behaviour, and thus in emotion.

Amygdala↗

Early amygdala damage disrupts performance on medial prefrontal cortex-related tasks but spares spatial learning and memory in the rat.

Recent studies have demonstrated that the postnatal development of connections between the basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) mature around postnatal days 13-15 (pd13-15), whereas these between the BLA and other structures such as the nucleus accumbens and the mediodorsal thalamus are completed by pd7. Accordingly, it is hypothesized that mPFC cytoarchitecture and hence its function may be specifically affected by neonatal (i.e. on pd7) but not later induced (i.e. on pd21) damage to the BLA. To test this hypothesis, rats received excitotoxic lesions to the BLA on either pd7 or pd21 and were subjected to two tests putatively sensitive to mPFC dysfunction, namely food hoarding and spontaneous alternation. In addition, rats were tested for spatial learning and memory, to determine any possible effects on hippocampal function. Consistent with the documented effects of mPFC lesions, pd7 damage to the BLA impaired spontaneous alternation and food hoarding performance, an effect that was not found in rats with BLA lesions induced on pd21. Spatial learning and memory, however, were not affected by the (neonatal) lesion procedure. Together, these results indicate that neonatal BLA damage affects species-specific sequential behavior and flexibility, which may be attributed to abnormal functioning of the mPFC.

Amygdala↗

Adaptation of the circular platform spatial memory task for mice: use in detecting cognitive impairment in the APP(SW) transgenic mouse model for Alzheimer's disease.

A methodology is described for use of a 16-hole circular platform task to test spatial memory in mice. Both bright light and a fan were used to motivate mice to escape the platform surface through a single hole containing an attached escape box. For each daily trial, three correlated measures (escape latency, number of errors, and error rating) comprehensively evaluated cognitive performance. In an initial study, the 'spatial' nature of this task was demonstrated by the much poorer performance of non-transgenic mice when visual cues are removed. Behavioral sensitivity of the circular platform task was then shown through its ability to discern cognitive impairment in 7-month-old transgenic mice, carrying the mutant APP(SW) gene for early-onset Alzheimer's disease in humans, from non-transgenic litter-mates. Since there are currently only a few tasks available to definitively test cognitive performance in mice, the circular platform task offers a versatile, multiple-measure option with numerous advantages. Particularly in view of the increasing number of genetically manipulated mouse models being produced, the circular platform task should be most useful in providing a sensitive evaluation of cognition in mice.

Alzheimer Disease↗

Sampling plans for fitting the psychometric function.

Research on estimation of a psychometric function psi has usually focused on comparing alternative algorithms to apply to the data, rarely addressing how best to gather the data themselves (i.e., what sampling plan best deploys the affordable number of trials). Simulation methods were used here to assess the performance of several sampling plans in yes-no and forced-choice tasks, including the QUEST method and several variants of up-down staircases and of the method of constant stimuli (MOCS). We also assessed the efficacy of four parameter estimation methods. Performance comparisons were based on analyses of usability (i.e., the percentage of times that a plan yields usable data for the estimation of all the parameters of psi) and of the resultant distributions of parameter estimates. Maximum likelihood turned out to be the best parameter estimation method. As for sampling plans, QUEST never exceeded 80% usability even when 1000 trials were administered and rendered accurate estimates of threshold but misestimated the remaining parameters. MOCS and up-down staircases yielded similar and acceptable usability (above 95% with 400-500 trials) and, although neither type of plan allowed estimating all parameters with optimal precision, each type appeared well suited to estimating a distinct subset of parameters. An analysis of the causes of this differential suitability allowed designing alternative sampling plans (all based on up-down staircases) for yes-no and forced-choice tasks. These alternative plans rendered near optimal distributions of estimates for all parameters. The results just described apply when the fitted psi has the same mathematical form as the actual psi generating the data; in case of form mismatch, all parameters except threshold were generally misestimated but the relative performance of all the sampling plans remained identical. Detailed practical recommendations are given.

Algorithms↗

Retrospective revaluation as simple associative learning.

Backward blocking, unovershadowing, and backward conditioned inhibition are examples of retrospective revaluation phenomena that have been suggested to involve more than simple associative learning. Models of these phenomena have thus used additional concepts, for example, appealing to attentional effects or more elaborate learning mechanisms. The author shows that a suitable representation of stimuli, paired with a careful analysis of the discriminations faced by animals, leads to an account of these and other phenomena in terms of a simple elemental model of associative learning, with essentially the same learning mechanism as the R. A. Rescorla and A. R. Wagner (1972) model. The author concludes with a discussion of some implications for theories of learning.

Animals↗

Behavioural abnormalities in a murine model of a human lysosomal storage disease.

The gusmps/gusmps mouse is a model of the human lysosomal storage disease mucopolysaccharidosis type VII due to deficient beta-glucuronidase activity. We now report behavioural abnormalities associated with this single gene defect. In grooming, a developmentally regulated and genetically based activity, the mutant mice spent 1-5% of the normal time for body grooming and about 60% of the normal time in face grooming when stimulated with a light water mist. In the Morris water maze which tests spatial learning, the mutants could learn to locate an invisible platform but were deficient in remembering its location the next day or developing strategies to locate it in new positions. Thus, the gusmps/gusmps mouse demonstrates behavioural, memory and cognitive deficiencies suitable for monitoring functional restorations in therapy.

Animals↗