Neuroscience
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Ketamine is a promising therapeutic for treatment-resistant depression (TRD) but is associated with an array of short-term psychomimetic side-effects. These disparate drug effects may be elicited through the modulation of neural circuit activity. The purpose of this study was to therefore delineate dose- and time-dependent changes in ketamine-induced neural oscillatory patterns in regions of the brain implicated in depression. ⋯ These low dose ketamine-induced oscillatory alterations were accompanied by a reduction in immobility time in the forced swim test. These results show that ketamine induces time-dependent effects on neural oscillations at specific frequencies. These drug-induced changes may differentially contribute to the psychomimetic and therapeutic effects of the drug.
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Store-operated Ca2+ entry (SOCE) contributes to Ca2+ refilling of endoplasmic reticulum (ER), but also provides Ca2+ influx involved in physiological and pathological signalling functions. Upon depletion of Ca2+ store, the sensor protein stromal interaction molecule (STIM) activates Orai1, forming an ion-conducting pore highly selective for Ca2+. SOCE-associated regulatory factor (SARAF) associates with STIM1 to facilitate a slow form of Ca2+-dependent inactivation of SOCE or interacts with Orai1 to stimulate SOCE in STIM1-independent manner. ⋯ The expression of Stim1 and SARAF, mainly localised in NeuN-immunopositive neurons, was reduced in the ischemic cortex. Interestingly, neuroprotection by ischemic PC prevented the reduction of SARAF expression in the lesioned cortex and this could be interpreted as a compensatory mechanism to restore ER Ca2+ refilling in neurons in the absence of STIM1. Thus, preventing SARAF downregulation may represent a pivotal mechanism implicated in neuroprotection provided by ischemic PC and should be exploited as an original target for novel stroke therapies.
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The pulvinar is a higher-order thalamic relay and a central component of the extrageniculate visual pathway, with input from the superior colliculus and visual cortex and output to all of visual cortex. Rodent pulvinar, more commonly called the lateral posterior nucleus (LP), consists of three highly-conserved subdivisions, and offers the advantage of simplicity in its study compared to more subdivided primate pulvinar. Little is known about receptive field properties of LP, let alone whether functional differences exist between different LP subdivisions, making it difficult to understand what visual information is relayed and what kinds of computations the pulvinar might support. ⋯ SIGNIFICANCE STATEMENT: The pulvinar has a perplexing role in visual cognition as no clear link has been found between the functional properties of its neurons and behavioral deficits that arise when it is damaged. The pulvinar, called the lateral posterior nucleus (LP) in rats, is a higher order thalamic relay with input from the superior colliculus and visual cortex and output to all of visual cortex. By characterizing single-cell response properties in anatomically distinct subdivisions we found two separate visual feature processing channels in the pulvinar, one in lateral LP related to higher speed processing which likely derives from superior colliculus input, and the other in rostromedial LP for motion processing derived through input from visual cortex.
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Animal studies suggest that the vestibular system autoregulates its sensitivity in response to prolonged low- or high-intensity motion in order to maintain an optimal working range. In humans, corresponding attenuations of vestibular responses after prolonged high-intensity motion exposure have been demonstrated. Here we explored whether a complementary increase in human vestibular sensitivity can be induced by motion conditioning at low-intensity, subliminal amplitudes. ⋯ Vestibular sensitivity for yaw rotations remained on average unaltered after IA conditioning indicating that sensitizing effects might be selective for the end-organ-specific vestibular pathways being stimulated during conditioning. These findings demonstrate that human vestibular sensitivity can be enhanced by subliminal sensory conditioning, similar to sensitizing effects observed in other sensory modalities. Conditioning-induced sensitization of vestibular responses may be an effective treatment for decrements in vestibular sensitivity in the elderly and patients with vestibular hypofunction.
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Photoreceptors are light-sensitive cells in the retina converting visual stimuli into electrochemical signals. These signals are evaluated and interpreted in the visual pathway, a process referred to as visual processing. Phosphodiesterase type 5 and 6 (PDE5 and 6) are abundant enzymes in retinal vessels and notably photoreceptors where PDE6 is exclusively present. ⋯ The effects of sildenafil were dependent on the wavelength condition in both assays. Our results support the observation that while PDE6 is a key player in phototransduction, near full inhibition of PDE6 is not enough to abolish the complex process of visual processing. Taken together, VEPs and SSVEPs are effective in demonstrating progressive effects of drug-induced changes in visual processing in rats and as the same paradigms may be applied in humans, representing a promising tool for translational research.