Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale
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Glutamate receptors responding to N-methyl-D: -aspartate (NMDA) are involved in neural development, excitotoxicity and neuronal plasticity. Each receptor includes at least two NR2 subunits. Here, we have examined the effects of selective antagonists of NR2A and NR2B subunits (NVP-AAM07 and Ro25-6981 respectively) on the effects of NMDA in the CA1 field of rat hippocampal slices. ⋯ NMDA-dependent long-term potentiation (LTP) induced by electrical stimulation was not prevented by Ro25-6981 but was prevented by selective blockade of the NR2A subunit. The results suggest that, at both presynaptic and postsynaptic sites in the rat hippocampus, NR2B-subunit-containing receptors limit NMDA receptor function by inhibitory restraint over NR2A-subunit-containing receptors, via calcineurin activation, and that LTP induction critically involves primarily receptors containing the NR2A subunit. Endogenous factors or drugs that modify this NR2B/NR2A interaction could have a major influence on synaptic transmission and plasticity in the brain.
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The synapsins are presynaptic membrane-associated proteins involved in neurotransmitter release. They are differentially expressed in tissues and cells of the central and peripheral nervous system. In vestibular end organs of mammals, synapsin I-like immunoreactivity has been reported in efferent and afferent terminals and in afferent nerve calyces surrounding type I hair cells. ⋯ Afferent endings are not labeled. Staining in hair cells is not associated with the synaptic ribbons, suggesting that there is an additional, non-synaptic role for the synapsins in some non-neuronal cells of vertebrates. Moreover, while the cristae of amniote and anamniote species share many functional attributes, differences in their synaptic vesicle-associated protein profiles appear to reflect their disparate hair cell populations.
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The role of the neutral amino acid glycine in excitotoxic neuronal injury is unclear. Glycine coactivates glutamate N-methyl-D-aspartate (NMDA) receptors by binding to a distinct recognition site on the NR1 subunit. Purely excitatory glycine receptors composed of NR1 and NR3/NR4 NMDA receptor subunits have recently been described, raising the possibility of excitotoxic effects mediated by glycine alone. ⋯ The toxic effects of high-dose glycine were comparable in extent to those produced by the excitatory amino acid glutamate in our model. When combined with sublethal hypoxia/hypoglycemia, the threshold of glycine toxicity was decreased to less than 1 mM, which corresponds to the range of concentrations of excitatory amino acids measured during in vivo cerebral ischemia. Taken together, these results further support the assumption of an active role of glycine in excitotoxic neuronal injury.
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Comparative Study
Facilitatory effects of 1 Hz rTMS in motor cortex of patients affected by migraine with aura.
We previously showed paradoxical facilitatory effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) on striate and extrastriate cortex of patients suffering migraine with aura. In this study we evaluated the effects of 1 Hz rTMS on the excitability of inhibitory and facilitatory circuits of motor cortex to explore whether the abnormal pattern of excitability extends beyond the sensory cortex also involving motor areas in migraine with aura. Nine patients affected by migraine with aura and eight healthy controls entered into the study. ⋯ Specifically, whereas intracortical facilitation (ICF) significantly decreased in controls, it significantly increased in migraineurs. ICI levels were not significantly affected by low-frequency stimulation. Our results showed that motor as well as sensory cortex of migraine patients present an abnormal modulation of cortical excitability, where a relevant role is likely played by the inefficiency of inhibitory circuits.
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Comparative Study
Blink effects on ongoing smooth pursuit eye movements in humans.
Blinks are known to affect eye movements, e.g., saccades, slow and fast vergence, and saccade-vergence interaction, in two ways: by superimposition of blink-associated eye movements and changes of the central premotor activity in the brainstem. The goal of this study was to determine, for the first time, the effects of trigeminal evoked blinks on ongoing smooth pursuit eye movements which could be related to visual sensory or premotor neuronal changes. This was compared to the effect of a target disappearing for 100-300 ms duration during ongoing smooth pursuit (blank paradigm) in order to control for the visual sensory effects of a blink. ⋯ However, small blinks that did not occlude the pupil (<10% of lid closure) also decreased smooth pursuit velocity. Thus, this blink effect on pursuit velocity cannot be explained by blink-associated eye movements or by the blink having blanked the visual input. We propose that part of this effect might either be caused by incomplete visual suppression during blinks and/or a change in the activity of omnipause neurons.