Neuroscience
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Patients with spatial hemi-neglect display systematic deviations of the subjective vertical. The magnitude of such deviations was shown to be modulated by internal factors mediating the perception of verticality, including head-orientation. The present study investigated whether and how spatial orientation deficits are modulated by external, contextual changes in neglect patients. ⋯ However, in the control groups, this modulation was only moderate whereas in the neglect group SVV judgments were substantially and systematically modulated by frame orientation: with CCW frame tilts, the spatial bias of neglect patients increased as a function of the magnitude of the tilt whereas with clockwise (CW) frame tilts, the spatial bias was decreased in case of moderate frame tilts and even reversed in case of stronger frame tilts, resulting in a substantial CW spatial bias. This dramatically enhanced RFE might be caused by a pathologically increased influence of contextual cues on the subjective vertical in neglect patients as a consequence of impaired processing of gravitational information. The results indicate a systematic bias of the subjective vertical along with an impairment of spatial orientation constancy which leads to severe perturbations of subjective space as well as an increased reliance on internal and external cues mediating the perception of verticality in neglect.
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Increased central corticotropin-releasing factor (CRF) signaling has been associated with various psychiatric symptoms, including anxiety, depression and psychosis. CRF signaling in both the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC) has been implicated in anxiety-like behavior. In addition, repeated activation of CRF receptors within the BLA induces a chronic anxious state. ⋯ In addition, the BLA may be involved in CRF-induced sensorimotor gating deficits. The absence of a long-term effect on these PPI deficits suggests that lasting activation of CRF receptors is a prerequisite for CRF-mediated effects on sensorimotor gating. The long-term effects of repeated CRF infusion on LES and acquisition of FPS on the other hand, show that in case of anxiety-related processes repeated CRF infusion may have lasting effects.
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The prefrontal cortex is highly vulnerable to traumatic brain injury (TBI) and its structural and/or functional alterations as a result of TBI can give rise to persistent working memory (WM) dysfunction. Using a rodent model of TBI, we have described profound WM deficits following TBI that are associated with increases in prefrontal catecholamine (both dopamine and norepinephrine) content. In this study, we examined if enhanced norepinephrine signaling contributes to TBI-associated WM dysfunction. ⋯ Chromatin immunoprecipitation (ChIP) assays using mPFC tissue from injured animals indicated increased phospho-CREB binding to the CRE sites of α1A, but not α1B, promoter compared to that observed in uninjured controls. To address the translatability of our findings, we tested the efficacy of the FDA-approved α1 antagonist Prazosin and observed that this drug improves WM in injured animals. Taken together, these studies suggest that enhanced CREB-mediated expression of α1 adrenoceptor contributes to TBI-associated WM dysfunction, and therapies aimed at reducing α1 signaling may be useful in the treatment of TBI-associated WM deficits in humans.
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Several lines of evidence suggest the existence of multiple progestin receptors that may account for rapid and delayed effects of progesterone in the CNS. The delayed effects have been long attributed to activation of the classical progestin receptor (Pgr). Recent studies have discovered novel progestin signaling molecules that may be responsible for rapid effects. ⋯ Analyses of adjacent brain sections showed that the highest expression of mRNAs encoding Pgr, Pgrmc1, Pgrmc2 and Serbp1 was detected in several hypothalamic nuclei important for female reproduction. In contrast, expression patterns of Paqr7 and Paqr8 were low and homogeneous in the hypothalamus, and more abundant in thalamic nuclei. The neuroanatomical distributions of these putative progestin signaling molecules suggest that Pgrmc1 and Pgrmc2 may play roles in neuroendocrine functions while Paqr7 and Paqr8 are more likely to regulate sensory and cognitive functions.
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The synthetic retinoid 13-cis-retinoic acid (13-cis-RA), prescribed for the treatment of severe nodular acne, has been linked to an increased incidence of depression. Chronic treatment studies in rodents have shown that 13-cis-RA induces an increase in depression-related behaviours and a functional uncoupling of the hippocampus and dorsal raphe nucleus (DRN). Changes in the number of serotoninergic neurons in the DRN have been reported in depressed human patients. ⋯ Similarly, changes in the density of serotoninergic neurons or in the volume of the MRN or DRN were not observed in 13-cis-RA treated animals. These data show that apoptotic actions of 13-cis-RA do not occur in vivo at drug concentrations that induce changes in depression-related behaviour and functional uncoupling of the DRN and hippocampus. The potential pro-depressant behavioural and molecular effects associated with chronic administration of 13-cis-RA may result from changes in serotoninergic activity rather than changes in the number of serotoninergic neurons.