Neuroscience
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Purkinje cell (PC) firing represents the sole output from the cerebellar cortex onto the deep cerebellar and vestibular nuclei. Here, we explored the different modes of PC firing in alert mice by extracellular recording. We confirm the existence of a tonic and/or bursting and quiescent modes corresponding to UP and DOWN state, respectively. ⋯ Complex spike (CS) frequency was increased during the 600-Hz buzz, indicating that this PC output actively contributes to the cerebello-olivary loop by triggering a disinhibition of the inferior olive. During the 600-Hz buzz, the first depolarizing component of the CS was reduced and the second depolarizing component was suppressed. Consistent with our experimental observations, using a 559-compartment single-PC model - in which PC UP state (of about -43mV) was obtained by the combined action of large tonic AMPA conductances and counterbalancing GABAergic inhibition - removal of this inhibition produced the 600-Hz buzz; the simulated buzz frequency decreased following an artificial CS.
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Morphologically mixed chemical/electrical synapses at axon terminals, with the electrical component formed by gap junctions, is common in the CNS of lower vertebrates. In mammalian CNS, evidence for morphologically mixed synapses has been obtained in only a few locations. Here, we used immunofluorescence approaches to examine the localization of the neuronally expressed gap junction forming protein connexin36 (Cx36) in relation to the axon terminal marker vesicular glutamate transporter-1 (vglut1) in the spinal cord and the trigeminal motor nucleus (Mo5) of rat and mouse. ⋯ Further, vglut1-terminals displaying Cx36-puncta were contacted by terminals labeled for glutamic acid decarboxylase65, which is known to be contained in presynaptic terminals on large-diameter primary afferents. Developmentally, mixed synapses begin to emerge in the spinal cord only after the second to third postnatal week and thereafter increase to adult levels. Our findings demonstrate that axon terminals of primary afferent origin form morphologically mixed synapses containing Cx36 in broadly distributed areas of adult rodent spinal cord and Mo5.
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It is well known that the H-reflex amplitude decreases during passive muscle lengthening in comparison with passive shortening. However, this decrease in spinal synaptic efficacy observed during passive lengthening seems to be lesser during eccentric voluntary contraction. The aim of the present study was to examine whether spinal excitability during lengthening condition could be modulated by magnetic brain stimulation. ⋯ Activation of the corticospinal pathway would partially cancel inhibitions caused by muscle stretch, and according to the time-delayed effect, this result suggested the existence of a specific polysynaptic pathway. In additional experiments, H responses were conditioned by cervico-medullary stimulations, showing that the modulation described by the previous results involves subcortical mechanisms. This study provides further evidences that the modulation of the final cortico-spinal command reaching the muscle depends on a central mechanism that controls peripheral input, such as Ia afference discharge during lengthening.
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Event-related potentials (ERPs) were recorded to explore, for the first time, the electrophysiological correlates of the taste-visual cross-modal Stroop effect. Eighteen healthy participants were presented with a taste stimulus and a food image, and asked to categorize the image as "sweet" or "sour" by pressing the relevant button as quickly as possible. Accurate categorization of the image was faster when it was presented with a congruent taste stimulus (e.g., sour taste/image of lemon) than with an incongruent one (e.g., sour taste/image of ice cream). ⋯ Dipole source analysis of the difference wave (incongruent minus congruent) indicated that two generators localized in the prefrontal cortex and the parahippocampal gyrus contributed to this taste-visual cross-modal Stroop effect. This result suggests that the prefrontal cortex is associated with the process of conflict control in the taste-visual cross-modal Stroop effect. Also, we speculate that the parahippocampal gyrus is associated with the process of discordant information in the taste-visual cross-modal Stroop effect.
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Mutation in presenilin 1 (PS1) is one of the leading causes of familial Alzheimer's disease (fAD). PS1 mutation exacerbates the autophagic and lysosomal pathology in AD patients, leading to accumulation of partially degraded material in bloated lysosomes and autophagosomes - a pathology that bears some resemblance to other diseases characterized by elevated lysosomal pH, like age-related macular degeneration. In this study, we examined the effect of the PS1-fAD mutation A246E on lysosomal pH and lysosomal function, and asked whether restoration of lysosomal pH could reverse some of these changes. ⋯ PS1-fAD fibroblasts had increased expression of ATP6V1B2, ATG5, BECN1 TFEB mRNA, and of ATP6V1B2, ATG5 and beclin at the protein level, consistent with chronic impairment of autophagic and lysosomal functions in the mutant cells. Critically, cyclic adenosine monophosphate (cAMP) treatment reacidified lysosomal pH in mutant PS1-fAD; cAMP also increased the availability of active cathepsin D and lowered the LC3B-II/-I ratio. These results confirm a small elevation in the lysosomal pH of human PS1-fAD fibroblasts, demonstrate that this lysosomal alkalization is associated with chronic changes in autophagy and degradation, and suggest that treatment to reacidify the lysosomes with cAMP can reverse these changes.