Kv3 potassium currents mediate rapid repolarisation of action potentials (APs), supporting fast spikes and high repetition rates. Of the four Kv3 gene family members, Kv3.1 and Kv3.3 are highly ...expressed in the auditory brainstem and we exploited this to test for subunit-specific roles at the calyx of Held presynaptic terminal in the mouse. Deletion of Kv3.3 (but not Kv3.1) reduced presynaptic Kv3 channel immunolabelling, increased presynaptic AP duration and facilitated excitatory transmitter release; which in turn enhanced short-term depression during high-frequency transmission. The response to sound was delayed in the Kv3.3KO, with higher spontaneous and lower evoked firing, thereby reducing signal-to-noise ratio. Computational modelling showed that the enhanced EPSC and short-term depression in the Kv3.3KO reflected increased vesicle release probability and accelerated activity-dependent vesicle replenishment. We conclude that Kv3.3 mediates fast repolarisation for short precise APs, conserving transmission during sustained high-frequency activity at this glutamatergic excitatory synapse.
Current anti-epileptic medications that boost synaptic inhibition are effective in reducing several types of epileptic seizure activity. Nevertheless, these drugs can generate significant ...side-effects and even paradoxical responses due to the broad nature of their action. Recently developed chemogenetic techniques provide the opportunity to pharmacologically recruit endogenous inhibitory mechanisms in a selective and circuit-specific manner. Here, we use chemogenetics to assess the potential of suppressing epileptiform activity by enhancing the synaptic output from three major interneuron populations in the rodent hippocampus: parvalbumin (PV), somatostatin (SST), and vasoactive intestinal peptide (VIP) expressing interneurons. To target different neuronal populations, promoter-specific cre-recombinase mice were combined with viral-mediated delivery of chemogenetic constructs. Targeted electrophysiological recordings were then conducted in an
model of chronic, drug-resistant epilepsy. In addition, behavioral video-scoring was performed in an
model of acutely triggered seizure activity. Pre-synaptic and post-synaptic whole cell recordings in brain slices revealed that each of the three interneuron types increase their firing rate and synaptic output following chemogenetic activation. However, the interneuron populations exhibited different effects on epileptiform discharges. Recruiting VIP interneurons did not change the total duration of epileptiform discharges. In contrast, recruiting SST or PV interneurons produced robust suppression of epileptiform synchronization. PV interneurons exhibited the strongest effect per cell, eliciting at least a fivefold greater reduction in epileptiform activity than the other cell types. Consistent with this, we found that
chemogenetic recruitment of PV interneurons suppressed convulsive behaviors by more than 80%. Our findings support the idea that selective chemogenetic enhancement of inhibitory synaptic pathways offers potential as an anti-seizure strategy.
The reactivity of an electroencephalogram (EEG) to external stimuli is impaired in comatose patients showing burst-suppression (BS) patterns following hypoxic–ischemic brain injury (HIBI). We ...explored the reactivity of BS induced by isoflurane in rat models of HIBI and controls using intermittent photic stimulation (IPS) delivered to one eye. The relative time spent in suppression referred to as the suppression ratio (SR) was measured on the contralateral fronto-occipital cortical EEG channel. The BS reactivity (BSR) was defined as the decrease in the SR during IPS from the baseline before stimulation (SRPRE). We found that BSR increased with SRPRE. To standardize by anesthetic depth, we derived the BSR index (BSRi) as BSR divided by SRPRE. We found that the BSRi was decreased at 3 days after transient global cerebral ischemia in rats, which is a model of brain injury after cardiac arrest. The BSRi was also reduced 2 months after experimental perinatal asphyxia in rats, a model of birth asphyxia, which is a frequent neonatal complication in humans. Furthermore, Oxytocin attenuated BSRi impairment, consistent with a neuroprotective effect in this model. Our data suggest that the BSRi is a promising translational marker in HIBI which should be considered in future neuroprotection studies.
Abstract
Sediment transport plays an important role in the overall process of navigation along the rivers, as it shapes the fairway continuously. This paper aims to present the partial results ...obtained in the PhD research regarding measures to be used in order to help stabilize the channel bed. The measures have been proposed and tested based on a calibrated and validated 2-dimensional hydrodynamic and sediment transport model. The results show the influence of the proposed measures along the river channel in comparison to the situation where no measures would be taken at all. Furthermore it can help understand the river and sediment dynamics in order to make the best decision upon the location, orientation, geometry and other properties of the proposed measures.
Disinformation and propaganda activities are a basic element in the successful conduct of the hybrid war in the acceptance of the Russian Federation. Considering the technological and, especially ...economic, gap between Russia and the other world powers (USA or China) Russian military strategists have concluded that the full exploitation of the advantages offered by the skillful use of the information power tool, may lead to the elimination of the disadvantages of the insufficient economic development of the country or of the deficient endowment of the Armed Forces with military technology of last generation in serial production. In the following pages we analyzed the most important aspects of the information war carried out by the Russian Federation, using the well-known media (Russia Today), during the conflict in Ukraine, focusing on the themes and contents specific to each of them.
The theory and applications of dynamic derivatives on time scales have recently received considerable interest. In this paper, we define a function using the combined diamond- α integral, investigate ...its monotonicity and give some refinements for Hölder's inequality. We present some applications for ℤ and ℝ.
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