Blockade of NR2B-Containing NMDA Receptors Prevents BDNF Enhancement of Glutamatergic Transmission in Hippocampal Neurons

Application of brain-derived neurotrophic factor (BDNF) to hippocampal neurons has profound effects on glutamatergic synaptic transmission. Both pre- and postsynaptic actions have been identified that depend on the age and type of preparation. To understand the nature of this diversity, we have begun to examine the mechanisms of BDNF action in cultured dissociated embryonic hippocampal neurons. Whole-cell patch-clamp recording during iontophoretic application of glutamate revealed that BDNF doubled the amplitude of induced inward current. Coexposure to BDNF and the NMDA receptor antagonist AP-5 markedly reduced, but did not entirely prevent, the increase in current. Coexposure to BDNF and ifenprodil, an NR2B subunit antagonist, reproduced the response observed with AP-5, suggesting BDNF primarily enhanced activity of NR2B-containing NMDA receptors with a lesser effect on non-NMDA receptors. Protein kinase involvement was confirmed with the broad spectrum inhibitor staurosporine, which prevented the response to BDNF. PKCI19-31 and H-89, selective antagonists of PKC and PKA, had no effect on the response to BDNF, whereas autocamtide-2-related inhibitory peptide, an antagonist of CaM kinase II, reduced response magnitude by 60%. These results demonstrate the predominant role of a specific NMDA receptor subtype in BDNF modulation of hippocampal synaptic transmission.     

Investigating the mechanisms of visually-evoked tactile sensations

When attempting to detect a near-threshold signal, participants often incorrectly report the presence of a signal, particularly when a stimulus in a different modality is presented. Here we investigated the effect of prior experience of bimodal visuotactile stimuli on the rate of falsely reported touches in the presence of a light. In Experiment 1, participants made more false alarms in light-present than light-absent trials, despite having no experience of the experimental visuotactile pairing. This suggests that light-evoked false alarms are a consequence of an existing association, rather than one learned during the experiment. In Experiment 2, we sought to manipulate the strength of the association through prior training, using supra-threshold tactile stimuli that were given a high or low association with the light. Both groups still exhibited an increased number of false alarms during light-present trials, however, the low association group made significantly fewer false alarms across conditions, and there was no corresponding group difference in the number of tactile stimuli correctly identified. Thus, while training did not affect the boosting of the tactile signal by the visual stimulus, the low association training affected perceptual decision-making more generally, leading to a lower number of illusory touch reports, independent of the light.     

Effects of parafoveal word length and orthographic features on initial fixation landing positions in reading

Previous research has demonstrated that readers use word length and word boundary information in targeting saccades into upcoming words while reading. Previous studies have also revealed that the initial landing positions for fixations on words are affected by parafoveal processing. In the present study, we examined the effects of word length and orthographic legality on targeting saccades into parafoveal words. Long (8?C9 letters) and short (4?C5 letters) target words, which were matched on lexical frequency and initial letter trigram, were paired and embedded into identical sentence frames. The gaze-contingent boundary paradigm (Rayner, 1975) was used to manipulate the parafoveal information available to the reader before direct fixation on the target word. The parafoveal preview was either identical to the target word or was a visually similar nonword. The nonword previews contained orthographically legal or orthographically illegal initial letters. The results showed that orthographic preprocessing of the word to the right of fixation affected eye movement targeting, regardless of word length. Additionally, the lexical status of an upcoming saccade target in the parafovea generally did not influence preprocessing.     

Reasoning strategies with rational numbers revealed by eye tracking

Recent research has begun to investigate the impact of different formats for rational numbers on the processes by which people make relational judgments about quantitative relations. DeWolf, Bassok, and Holyoak (Journal of Experimental Psychology: General, 144(1), 127–150, 2015) found that accuracy on a relation identification task was highest when fractions were presented with countable sets, whereas accuracy was relatively low for all conditions where decimals were presented. However, it is unclear what processing strategies underlie these disparities in accuracy. We report an experiment that used eye-tracking methods to externalize the strategies that are evoked by different types of rational numbers for different types of quantities (discrete vs. continuous). Results showed that eye-movement behavior during the task was jointly determined by image and number format. Discrete images elicited a counting strategy for both fractions and decimals, but this strategy led to higher accuracy only for fractions. Continuous images encouraged magnitude estimation and comparison, but to a greater degree for decimals than fractions. This strategy led to decreased accuracy for both number formats. By analyzing participants’ eye movements when they viewed a relational context and made decisions, we were able to obtain an externalized representation of the strategic choices evoked by different ontological types of entities and different types of rational numbers. Our findings using eye-tracking measures enable us to go beyond previous studies based on accuracy data alone, demonstrating that quantitative properties of images and the different formats for rational numbers jointly influence strategies that generate eye-movement behavior.     

A randomized controlled trial of a peer support intervention targeting antiretroviral medication adherence and depressive symptomatology in HIV-positive men and women.

OBJECTIVE: To determine the efficacy of a peer-led social support intervention involving support groups and telephone contacts compared with standard clinical care to enhance antiretroviral medication adherence. DESIGN: Randomized controlled trial with follow-up. Participants were 136 HIV-positive indigent mainly African American and Puerto Rican men and women recruited from an outpatient clinic in the Bronx, New York. The 3-month intervention was delivered by other HIV-positive clinic patients trained in addressing barriers to adherence and sensitively providing appraisal, spiritual, emotional, and informational adherence-related social support. MAIN OUTCOME MEASURES: Medical chart-abstracted HIV-1 RNA viral load, antiretroviral adherence according to electronic drug monitoring and participant self-report, and social support and depressive symptomatology. All assessments conducted at baseline, 3 months, and 6 months. RESULTS: Intent-to-treat and as-treated analyses indicated no between-conditions intervention effects on the primary outcome of HIV-1 RNA viral load or any of the secondary outcomes at immediate postintervention or follow-up. Post hoc analyses within the intervention condition indicated greater intervention exposure was associated with higher self-reported adherence, higher social support, and lower depressive symptomatology at follow-up, even after controlling for baseline adherence. CONCLUSION: Null findings, consistent with the limited literature on efficacious highly active antiretroviral therapy (HAART) adherence interventions, may be due to insufficient exposure to the intervention, its low intensity, or the nature of the sample-a heterogeneous HAART-experienced group of patients with high levels of substance use and multiple other competing stressors. Overall, findings highlight the need for more comprehensive and intensive efforts to battle nonadherence.     

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Hypothalamo-Pituitary-Adrenocortical Regulation Following Lesions of the Central Nucleus of the Amygdala

Previous reports indicate that the central nucleus of the amygdala (CeA) stimulates adrenocorticotropin and corticosterone secretion, suggesting a role for this region in central hypothalamo-pituitary-adrenocortical (HPA) stress regulation. To evaluate this hypothesis, this study assessed the impact of CeA lesion on the response of hypophysiotrophic paraventricular nucleus (PVN) neurons to acute restraint and chronic unpredictable stress exposure. In contrast to previous reports, CeA lesions did not affect corticosterone or ACTH secretion induced by acute stress. Acute restraint increased PVN corticotropin releasing hormone (CRH) mRNA expression, increased the number of parvocellular PVN neurons expressing the co-secretagogue arginine vasopressin (AVP), and induced cFOS mRNA expression in the parvocellular PVN. However, there was no additional effect of CeA lesion on any measure of PVN activation. Chronic unpredictable stress exposure induced long-term activation of the HPA axis, noted by thymic involution, adrenal hypertrophy and increased PVN CRH mRNA expression. Stress-induced changes in thymus and adrenal weights were not affected by CeA lesion. Further, CeA lesion rats did not differ from controls in post-stress CRH mRNA expression. However, basal CRH mRNA expression was increased in the PVN of CeA rats, suggesting that the CeA plays a role in long-term inhibition of the PVN. The results of these studies are not consistent with the hypothesis that the CeA is necessary for stress-induced pituitary-adrenocortical activation. Rather, this region may play a stressor-specific modulatory role in regulation of HPA function.     

The Spinal Cord Injured Revisited: The Relationship Between Self-Blame, Other-Blame and Coping

Self-blame has been viewed as functional for victims' adjustment to negative life events. This perspective has been primarily based on the findings of Bulman and Wortman's 1977 study of the spinal cord injured. The present study replicates and extends the Bulman and Wortman study, using similar measures on a comparable sample and comparable life event. Patients did not differentiate among the concepts of responsibility, fault, and blame for the cause of the accident. Patients were behavioral rather than characterological self-blaming and alcohol use prior to the accident was the best predictor of self-blame. Attributions of responsibility for the cause of the event versus responsibility for rehabilitation (sequelae of the event) did not distinguish effective from ineffective copers. Bulman and Wortman's (1977) single-item measure of coping correlated with this study's multidimensional assessment of coping. There was no relationship between patients' attributions of self-blame and nurse's ratings of patients' coping but other-blame was associated with poorer coping.     

Motivation for and commitment to social values: The roles of age and gender

The primary aim of this study was to examine how motives and commitment to social values influence well-being in men and women of different ages. College students and older adults in the community reported on their motivational orientation (intrinsic vs. extrinsic), behavioral commitment to idiographic social values, and their current well-being (satisfaction with life, positive and negative affect). We tested a series of path models with motivational orientation mediating the relationship between commitment to values and well-being. Consistent with self-determination theory, we found that behavioral commitment to intrinsically motivating social values was related to greater life satisfaction and positive affect, whereas being committed to extrinsically motivating values was related to greater negative affect. While age and gender did not moderate these relationships, meaningful age and gender differences emerged across value-based motivations, commitment, and indices of well-being. This work adds to our understanding of how values are a guiding influence for successful navigation of one’s social world.