Brain research
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The mechanisms by which agonists and other ligands bind ligand-gated ion channels are important determinants of function in neurotransmitter receptors. The partial agonist, kainic acid (KA) activates a less desensitized, and more robust AMPA receptor (AMPAR) current than full agonists, glutamate or AMPA. Cyclothiazide (CTZ), the allosteric modulator of AMPARs, potentiates receptor currents by inhibiting receptor desensitization resulting from agonist activation. ⋯ The potency of glutamate and KA activation of GluR1A782N was not significantly different from that of the wild-type GluR1 receptor although the mutant receptor currents were more sensitive to CTZ potentiation than the wild-type receptor current. This result is an indication that glutamate and KA binding to the agonist (S1/S2) domain on AMPAR can be modulated by an expendable splice-variable region of the receptor. Moreover, the effect of the allosteric modulator, CTZ on agonist activation of AMPAR can also be modified by a non-conserved amino acid residue substitution within the splice-variable "flip/flop" region.
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Neuronal differentiation and neurite outgrowth are key processes during development of the nervous system. Understanding the regulation of neurite outgrowth stimulated by neurotrophins is crucial to developing therapies to promote axon regeneration after injury or in neurodegenerative diseases. Treatment of PC12 cells with nerve growth factor (NGF) stimulates them to extend neurites and differentiate into a sympathetic neuron-like phenotype. ⋯ Inhibition of p38 MAPK signalling with SB202190 blocked phosphorylation of Hsp25 without affecting NGF-induced neurite outgrowth or the heat shock-dependent enhancement of elongation. These findings indicate that Hsp25 is not required for NGF-induced neurite outgrowth in PC12 cells and is not responsible for the heat shock-enhancement of NGF-induced neurite elongation. Instead, inhibition of MEK1/2 with U0126 partially reduced the heat shock-enhancement of NGF-stimulated neurite elongation.
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We report first results of a multilevel, cross-modal study on the neuronal mechanisms underlying auditory sequential streaming, with the focus on the impact of visual sequences on perceptually ambiguous tone sequences which can either be perceived as two separate streams or one alternating stream. We combined two psychophysical experiments performed on humans and monkeys with two human brain imaging experiments which allow to obtain complementary information on brain activation with high spatial (fMRI) and high temporal (MEG) resolution. ⋯ Thus, comparable to an explicit instruction, this approach can be used to control the subject's perceptual organization of an ambiguous sound sequence without the need for the subject to directly report it. This finding is of particular importance for animal studies because it allows to compare electrophysiological responses of auditory cortex neurons to the same acoustic stimulus sequence eliciting either a segregated or integrated percept.
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Auditory perception comprises bottom-up as well as top-down processes. While research in the past has revealed many neural correlates of bottom-up processes, less is known about top-down modulation. Memory processes have recently been associated with oscillations in the gamma-band of human EEG (30 Hz and above) which are enhanced when incoming information matches a stored memory template. ⋯ Analysis of evoked gamma-band responses yielded no significant task-dependent modulation, but we observed a stimulus dependency, which was also present in a control experiment: The amplitude of evoked gamma responses showed an inverted U-shape as a function of stimulus frequency. Investigation of total gamma activity revealed functionally relevant responses at high frequencies (90 Hz to 250 Hz), which showed significant modulations by matches with STM: Complete matches led to the strongest enhancements (starting around 100 ms after stimulus onset) and partial matches resulted in intermediate ones. The results support the conclusion that very high frequency oscillations (VHFOs) are markers of active stimulus discrimination in STM matching processes and are attributable to higher cognitive functions.
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Recent studies have shown a close correspondence between perceptual detection thresholds for sounds in quiet and a measure of neuronal thresholds derived from the stimulus-dependent timing of the first spike of auditory-nerve fibers. In addition, stimulus properties might be encoded by differences in first-spike timing of neurons in the central auditory system. ⋯ Two of the 5 parameters can be considered constant (at least for the vast majority of fibers), while the other 3 vary in meaningful ways with the fibers' spontaneous discharge rates. The elements of the model and some implications are discussed.