Neuroscience
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Glycine transporter 1 (GlyT1) mediates the termination of inhibitory glycinergic receptor signaling in the spinal cord and brainstem, and is also present diffusely in the forebrain. Here, it regulates the ambient glycine concentration and influences the 'glycine' site occupancy of N-methyl-d-aspartate receptors (NMDARs). GlyT1 is a reversible transporter with a substantial, but not excessive, sodium-motive force for uphill transport. ⋯ These two glycine release mechanisms can be distinguished by their voltage dependence, as the reversed-uptake cycle decreases at hyperpolarized potentials, whereas heteroexchange electroneutrality preserves glycine efflux and NMDAR activation at these potentials. These results establish GlyT1-mediated efflux as a positive regulator of NMDAR coagonist site occupancy, and demonstrate the efficacy of sarcosine heteroexchange in enhancing coagonist site occupancy. Because NMDAR facilitation by GlyT1-inhibitors and sarcosine relies on different transport mechanisms, their actions may be a source of variability in reversing NMDAR hypofunction in schizophrenia.
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Research suggests that locomotion may be primarily caused by shifting stable body balance from one location in the environment to another with subsequent rhythmical muscle activation by the central pattern generator (CPG), constituting a multi-level control system. All levels interact with environmental forces affected by proprioceptive and vestibular reflexes as well as vision. A similar multi-level control schema is likely used to shift body balance laterally when the body weight is rhythmically transferred from side-to-side. ⋯ The purpose of the present study was to verify if it was also applicable to locomotor tasks in other directions such as sidestepping. We predicted that during sidestepping, the actual and referent posture can transiently match each other bringing the activity of multiple muscles to a minimum. The existence of such minima was demonstrated in healthy adults performing three locomotor tasks involving shifts of the body weight from side-to-side thus further supporting the validity of the multi-level control scheme of locomotion.