Increased activity of D2 receptors (D2Rs) in the striatum has been linked to the pathophysiology of schizophrenia. To determine directly the behavioral and physiological consequences of increased D2R function in the striatum, we generated mice with reversibly increased levels of D2Rs restricted to the striatum. D2 transgenic mice exhibit selective cognitive impairments in working memory tasks and behavioral flexibility without more general cognitive deficits. The deficit in the working memory task persists even after the transgene has been switched off, indicating that it results not from continued overexpression of D2Rs but from excess expression during development. To determine the effects that may mediate the observed cognitive deficits, we analyzed the prefrontal cortex, the brain structure mainly associated with working memory. We found that D2R overexpression in the striatum impacts dopamine levels, rates of dopamine turnover, and activation of D1 receptors in the prefrontal cortex, measures that are critical for working memory.
Psychotherapy is used commonly to treat a variety of mental illnesses, yet surprisingly little is known about its biological mechanisms especially in comparison with pharmacotherapy. In this review we survey the current knowledge about changes in brain function following psychotherapeutic intervention that are detectable with current neuroimaging techniques. We also consider the possible role for neuroimaging in refining clinical diagnoses and predicting treatment outcome, which would benefit both clinical decision-making and the cognitive neuroscience of psychotherapy.
The present series of experiments assessed how information from the whiskers controls and modulates infant rat behavior during early learning and attachment. Passive vibrissal stimulation can elicit behavioral activity in pups throughout the first two postnatal weeks, although orienting to the source of stimulation is evident only after ontogenetic emergence of whisking. In addition, while pups were capable of demonstrating learning in a classical conditioning paradigm pairing vibrissa stimulation with electric shock, no corresponding changes were detected in the anatomy of the barrel cortex as determined by cytochrome oxidase (CO) staining. Finally, the role of whiskers in a more naturalistic setting was determined in postnatal day (PN)3-5 and PN11-12 pups. Our results showed that both nipple attachment and huddling were disrupted in whisker-clipped PN3-5 pups but only marginally altered in PN11-12 pups. Together, these results suggest that the neonatal whisker system is behaviorally functional and relevant for normal mother-infant interactions, though it lacks the sophistication of a mature whisker system that evokes very specific and directed responses.
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