Search

A fundamental property of extinction is that the behavior that is suppressed during extinction can be unmasked through a number of postextinction procedures. Of the commonly studied unmasking procedures (spontaneous recovery, reinstatement, contextual renewal, and rapid reacquisition), rapid reacquisition is the only approach that allows a direct comparison between the impact of a conditioning trial before or after extinction. Thus, it provides an opportunity to evaluate the ways in which extinction changes a subsequent learning experience. In five experiments, we investigate the behavioral and neurobiological mechanisms of postextinction reconditioning. We show that rapid reconditioning of unsignaled contextual fear after extinction in male Long–Evans rats is associative and not affected by the number or duration of extinction sessions that we examined. We then evaluate c-Fos expression and histone acetylation (H4K8) in the hippocampus, amygdala, prefrontal cortex, and bed nucleus of the stria terminalis. We find that in general, initial conditioning has a stronger impact on c-Fos expression and acetylation than does reconditioning after extinction. We discuss implications of these results for theories of extinction and the neurobiology of conditioning and extinction.

Homer postsynaptic scaffolding proteins regulate forebrain glutamate transmission and thus, are likely molecular candidates mediating hypofrontality in addiction. Protracted withdrawal from cocaine experience increases the relative expression of Homer2 versus Homer1 isoforms within medial prefrontal cortex (mPFC). Thus, this study used virus-mediated gene transfer strategies to investigate the functional relevance of an imbalance in mPFC Homer1/2 expression as it relates to various measures of sensorimotor, cognitive, emotional and motivational processing, as well as accompanying alterations in extracellular glutamate in C57BL/6J mice. mPFC Homer2b overexpression elevated basal glutamate content and blunted cocaine-induced glutamate release within the mPFC, whereas Homer2b knockdown produced the opposite effects. Despite altering mPFC glutamate, Homer2b knockdown failed to influence cocaine-elicited conditioned place preferences, nor did it produce consistent effects on any other behavioral measures. In contrast, elevating the relative expression of Homer2b versus Homer1 within mPFC, by overexpressing Homer2b or knocking down Homer1c, shifted the dose-response function for cocaine-conditioned reward to the left, without affecting cocaine locomotion or sensitization. Intriguingly, both these transgenic manipulations produced glutamate anomalies within the nucleus accumbens (NAC) of cocaine-naive animals that are reminiscent of those observed in cocaine experienced animals, including reduced basal extracellular glutamate content, reduced Homer1/2 and glutamate receptor expression, and augmented cocaine-elicited glutamate release. Together, these data provide novel evidence in support of opposing roles for constitutively expressed Homer1 and Homer2 isoforms in regulating mPFC glutamate transmissionin vivoand support the hypothesis that cocaine-elicited increases in the relative amount of mPFC Homer2 versus Homer1 signaling produces abnormalities in NAC glutamate transmission that enhance vulnerability to cocaine reward.

Annie dreaded what would happen next--she had been down this road many times before. There she was--minding her own business, just wanting to watch a movie like any normal person--when she noticed her breathing was off. Immediately she began to monitor her breathing and soon it seemed as if she just could not get enough air. She remembered a recent visit to the ER when the nurse patiently showed her that the oxygen saturation levels were good. She remembered, but it didn't help. It wasn't that she believed this time was different--that this time she was going to suffocate. No, that might be a textbook explanation but it wasn't her explanation. She just couldn't breathe, and knowing that "it was all in her head" just didn't seem to help. Soon she would be spiraling into symptoms that, like an Old Testament prophet, would beget more apprehension, which would beget more symptoms--palpitations, dizziness, a fear of fainting, trembling, feeling that things around her were unreal, fear of going crazy--which would beget more dread. Worst of all, she feared looking foolish. What if she fainted right there in the movie theater? What if she lost control and started gulping big chunks of air down? What if she...? What would they think of her? ********** Annie's experience may be a little different from others' who suffer from panic disorder, but not too different. For some, panic attacks may occur in specific situations or in certain types of environments while for others these attacks come out of the blue. The final common pathway, however, is not unique--it is pure human misery. It is not uncommon to find talented men and women who live truncated lives because of panic attacks, the fear of having a panic attack, and the fear of the fear of having a panic attack. Overview of Panic Disorders Panic disorder is one of the most studied anxiety disorders. While about 25% of Americans suffer from anxiety, only a small subgroup will ever be diagnosed with panic disorder (Dugue & Neugroschl, 2002). Clark (1986) described panic attacks as "an intense feeling of apprehension or impending doom which is of sudden onset and which is associated with a wide range of distressing physical sensations" (p. 461). These physical sensations include all those exhibited by Annie as well as a number of other symptoms (Table 1). According to established criteria, at least four of these symptoms must occur abruptly and peak within 10 minutes (American Psychiatric Association [APA], 2000). Lifetime prevalence rates for panic disorder are thought to be between 1% and 3.5%, with significantly higher prevalence rates found in general medical settings (e.g., patients with chest pain, asthma, headaches, epilepsy) (APA, 2000; Plewa, 2002). Prevalence is higher for women (2:1). Panic disorder results in considerable morbidity (e.g., 10%-20% attempt suicide, 7%-28% have history of substance abuse) and increased mortality (Malizia et al., 1998; Plewa). A considerable variance occurs among individuals related to frequency of "attacks" and course of illness. Many, but not all, patients report a lifelong history of anxiety before the actual diagnosis of panic disorder is made. A bimodal distribution of onset can be predicted with first panic attacks occurring during late adolescence or during the mid 30s. The majority of patients report their first panic attack happening "out of the blue," but subsequent attacks are often attached to situational or environmental stimuli. Elderly individuals are less likely than younger people to suffer from panic attacks, with a number of competing hypotheses generated from this observation. Individuals with a family history of panic attacks are more likely to suffer from panic attacks themselves than is the general population, suggesting a genetic contribution. Finally, a history of childhood separation anxiety correlates to adult panic disorder. Models for Panic Disorders Historically, both psychologic and biologic models for panic disorders have been advanced in the literature. …

Children with severe and multiple disabilities constitute a heterogeneous population that typically experiences significant and lifelong difficulties in learning to read and write. These difficulties appear to be both intrinsic and environmental in nature. Children with severe and multiple disabilities struggle particularly with vocabulary acquisition and phonological awareness. Home, preschool, and school environments may limit literacy learning opportunities by making literacy a lower priority than the child's competing health, self-care, and therapeutic needs; by providing limited access to adapted print materials or tools; by providing limited access to communication supports; or by providing little time for literacy learning. Children with severe and multiple disabilities who have demonstrated literacy learning progress are often taught in technology-supported environments offering a wide range of word study, text-based reading and writing instruction, and opportunities for print exploration. Sufficient evidence exists for clinicians and educators to begin providing more successful literacy instruction to individual children and classrooms by comparing their children and intervention contexts with those reported in the limited body of research in this area.