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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In the mammalian retina, excitotoxicity has been shown to be involved in apoptotic retinal ganglion cell (RGC) death and is associated with certain retinal disease states including glaucoma, diabetic retinopathy and retinal ischemia. Previous studies from this lab [Wehrwein E, Thompson SA, Coulibaly SF, Linn DM, Linn CL (2004) Invest Ophthalmol Vis Sci 45:1531-1543] have demonstrated that acetylcholine (ACh) and nicotine protects against glutamate-induced excitotoxicity in isolated adult pig RGCs through nicotinic acetylcholine receptors (nAChRs). Activation of nAChRs in these RGCs triggers cell survival signaling pathways and inhibits apoptotic enzymes [Asomugha CO, Linn DM, Linn CL (2010) J Neurochem 112:214-226]. ⋯ In these studies, a preconditioning dose of calcium was introduced to cells using a variety of mechanisms before a large glutamate insult was applied to cells. Results from these studies support the hypothesis that preconditioning cells with a relatively low level of calcium before an excitotoxic insult leads to neuroprotection. In the future, these results could provide important information concerning therapeutic agents developed to combat various diseases involved with glutamate-induced excitotoxicity.
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The medial thalamic parafascicular nucleus (PF) and the rostral anterior cingulate cortex (rACC) are implicated in the processing and suppression of the affective dimension of pain. The present study evaluated the functional interaction between PF and rACC in mediating the suppression of pain affect in rats following administration of morphine or carbachol (acetylcholine agonist) into PF. Vocalizations that occur following a brief noxious tailshock (vocalization afterdischarges) are a validated rodent model of pain affect, and were preferentially suppressed by injection of morphine or carbachol into PF. ⋯ Blocking glutamate receptors in rACC (NMDA and non-NMDA) by injecting D-2-amino-5-phosphonovalerate (AP-5) or 6-cyano-7-nitroquinoxaline-2,3-dione disodium (CNQX) produced dose-dependent antagonism of morphine-induced increases in vocalization thresholds. Carbachol-induced increases in vocalization thresholds were not affected by injection of either glutamate receptor antagonist into rACC. The results demonstrate that glutamate receptors in the rACC contribute to the suppression of pain affect produced by injection of morphine into PF, but not to the suppression of pain affect generated by intra-PF injection of carbachol.
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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.