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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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.
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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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Comparative Study
Timbre discrimination in normal-hearing and hearing-impaired listeners under different noise conditions.
In an attempt to quantify differences in object separation and timbre discrimination between normal-hearing and hearing-impaired listeners with a moderate sensorineural hearing loss of two different configurations, psychoacoustic measurements were performed with a total of 50 listeners. The experiments determined just noticeable differences (JND) of timbre in normal-hearing and hearing-impaired subjects along continua of "morphed" musical instruments and investigated the variance of JND in silence and different background noise conditions and on different sound levels. ⋯ In the condition testing, transferability from silence to noise (i.e., the ability to imagine how the stimulus heard in silence would sound in noise), no significant JND differences across listener groups were found. The results can be explained by primary factors involved in sensorineural hearing loss and contradict the hypothesis that hearing-impaired people generally have more problems in object discrimination than normal-hearing people.