Neuroscience
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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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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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The cerebellum, which controls coordinated and rapid movements, is a potential target for the deleterious effects of drugs of abuse including cannabis (i.e. marijuana, cannabinoids). Prenatal exposure to cannabinoids has been documented to cause abnormalities in motor and cognitive development, but the exact mechanism of this effect at the cellular level has not been fully elucidated. Previous studies indicate that cannabinoids are capable of modulating synaptic neurotransmission. ⋯ WIN treatment of pregnant rats also profoundly affected the intrinsic properties of Purkinje neurons in offspring. This treatment increased the firing regularity, firing frequency, amplitude of afterhyperpolarization (AHP), the peak amplitude of action potential and the first spike latency, but decreased significantly the time to peak and duration of action potentials, the instantaneous firing frequency, the rate of rebound action potential and the voltage "sag" ratio. These results raise the possibility that maternal exposure to cannabinoids may profoundly affect the intrinsic membrane properties of cerebellar Purkinje neurons of offspring by altering the membrane excitability through modulation of intrinsic ion channels.
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Sensory neurons display transient changes in their response properties following prolonged exposure to an appropriate stimulus (adaptation). In adult cat primary visual cortex, spatial frequency-selective neurons shift their preferred spatial frequency (SF) after being adapted to a non-preferred SF. In anesthetized cats prepared for electrophysiological recordings in the visual cortex, we applied a non-preferred spatial frequency for two successive periods of adaptation (a recovery and interval of ∼90 min separated both phases of adaptation) in order to determine if a first adaptation retained an influence on a second adaptation. ⋯ The supplementary response changes suggest that neurons in area 17 keep a "memory" trace of the previous stimulus properties. It also highlights the dynamic nature of basic neuronal properties in adult cortex since repeated adaptations modified both the spatial frequency tuning selectivity and the response strength to the preferred spatial frequency. These enhanced neuronal responses suggest that the range of adaptation-induced plasticity available to the visual system is broader than anticipated.
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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.