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Behavioral and associative effects of differential outcomes in discrimination learning.

The role of the reinforcer in instrumental discriminations has often been viewed as that of facilitating associative learning between a reinforced response and the discriminative stimulus that occasions it. The differential-outcome paradigm introduced by Trapold (1970), however, has provided compelling evidence that reinforcers are also part of what is learned in discrimination tasks. Specifically, when the availability of different reinforcing outcomes is signaled by different discriminative stimuli, the conditioned anticipation of those outcomes can provide another source of stimulus control over responding. This article reviews how such control develops and how it can be revealed, its impact on behavior, and different possible mechanisms that could mediate the behavioral effects. The main conclusion is that differential-outcome effects are almost entirely explicable in terms of the cue properties of outcome expectancies-namely, that conditioned expectancies acquire discriminative control just like any other discriminative or conditional stimulus in instrumental learning.

Animals↗

Y-chromosomal effects on discrimination learning and hippocampal asymmetry in mice.

From a four-way cross between unrelated inbred strains of mice, a random-breeding line was developed that segregated at two coat-color loci and carried Y chromosomes from different sources. Adult males were used for measurements of black-white discrimination learning and 7-day response retention in a water maze, body weight, brain weight, and left- and right-side hippocampus weight. Clear evidence was obtained of Y-linked influences on response acquisition, body weight, right-side hippocampus weight, and hippocampal asymmetry, whereas direct effects of autosome 9 were indicated with regard to right-side hippocampus weight only. However, epistatic interactions of the Y chromosome with autosome 9 were found for response acquisition and body weight and with autosome 4 for hippocampal asymmetry.

Animals↗

Different hippocampal activity profiles for PKA and PKC in spatial discrimination learning.

Protein kinases are considered essential for the processing and storage of information in the brain. However, the dynamics of protein kinase activation in the hippocampus during spatial learning are poorly understood. In this study, rats were trained to learn a holeboard spatial discrinmination task and the activity profiles for cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) and Ca2+/ phospholipid-dependent protein kinase C (PKC) in the hippocampus were examined. Hippocampal PKA activity increased rapidly on Day 1 of spatial learning and remained moderately high at later stages of acquisition. In contrast, PKC activity increased in particulate fractions compared with cytosolic fractions after habituation training and was maximal at Day 3 of spatial acquisition. The results establish a temporal dissociation between PKA and PKC during acquisition of spatial discrimination learning.

Animals↗

Hippocampal gene expression profiling in spatial discrimination learning.

Learning and long-term memory are thought to involve temporally defined changes in gene expression that lead to the strengthening of synaptic connections in selected brain regions. We used cDNA microarrays to study hippocampal gene expression in animals trained in a spatial discrimination-learning paradigm. Our analysis identified 19 genes that showed statistically significant changes in expression when comparing Nai;ve versus Trained animals. We confirmed the changes in expression for the genes encoding the nuclear protein prothymosin(alpha) and the delta-1 opioid receptor (DOR1) by Northern blotting or in situ hybridization. In additional studies, laser-capture microdissection (LCM) allowed us to obtain enriched neuronal populations from the dentate gyrus, CA1, and CA3 subregions of the hippocampus from Nai;ve, Pseudotrained, and spatially Trained animals. Real-time PCR examined the spatial learning specificity of hippocampal modulation of the genes encoding protein kinase B (PKB, also known as Akt), protein kinase C(delta) (PKC(delta)), cell adhesion kinase(beta) (CAK(beta), also known as Pyk2), and receptor protein tyrosine phosphatase(zeta/beta) (RPTP(zeta/beta)). These studies showed subregion specificity of spatial learning-induced changes in gene expression within the hippocampus, a feature that was particular to each gene studied. We suggest that statistically valid gene expression profiles generated with cDNA microarrays may provide important insights as to the cellular and molecular events subserving learning and memory processes in the brain.

Animals↗

The effects of haloperidol on discrimination learning and behavioral symptoms in autistic children.

This double-blind and placebo-controlled clinical trial in autistic children had three objectives: (a) to replicate earlier findings that haloperidol administration is associated with a significant reduction of behavioral symptoms; (b) to further assess its safety when given on a short-term basis; and (c) to assess whether it has an effect on discrimination learning. Forty-five children, 2.02 to 7.58 years old (M = 4.49), completed this crossover design, with random assignment to treatment sequences. Haloperidol was shown to be a powerful therapeutic agent when administered for 4 weeks and free of side effects; at doses ranging from 0.25 to 4.0 mg/day (M = 0.844), there was a clinically and statistically significant reduction of a variety of symptoms. Under the given conditions, the children failed to learn on either haloperidol or placebo.

Autistic Disorder↗

Interaction between the cholinergic system and CRH in the modulation of spatial discrimination learning in mice.

Both cholinergic and CRH systems have been linked to cognitive processes such as learning and memory, and neuroanatomical as well as neurochemical evidence suggests important interactions between these two systems. Moreover, recent reports of pro-mnestic effects of CRH open the possibility that CRH could have beneficial effects in animals with cholinergic dysfunction. In a first experiment, spatial discrimination of C57BL/6 mice treated with various doses of scopolamine (0.5--2.0 mg/kg IP) was tested in a two-choice water maze task. Scopolamine, but not methylscopolamine, impaired accuracy and decreased responsivity. In contrast, similar doses of the nicotinic antagonist mecamylamine had no effect on choice accuracy but altered responsivity, as indicated by increased errors of omission and a reduction in swim speed during early experimental stages. ICV CRH (0.5--1.0 microg) also failed to significantly affect accuracy, but a strong tendency was observed to impair percentage correct responses. Measures of responsivity, such as errors of omission, choice latency and distance traveled, and of thigmotaxis were not significantly affected by CRH. However, initial swim speed was reduced by the peptide. Combined treatment with scopolamine (0.5 mg/kg IP) and CRH (0.5 microg ICV) had only mild, and primarily independent, effects, but overall suggested that concomitant blockade of muscarinic receptors and activation of the CRH system would rather act synergistically to disrupt spatial discrimination learning. Synergistic effects were also observed when animals receiving a combination of mecamylamine (2.0 mg/kg IP) and CRH (0.5 microg ICV) were tested, both in terms of responsivity and thigmotaxis, and there was limited evidence that part of these effects were potentiating. Thus, the cholinergic and CRH systems interact in the modulation of learning, but CRH, contrary to prediction, worsens the impairment caused by cholinergic blockade.

Acetylcholine↗