ObjectiveDisrupting thalamocortical activity patterns has proven to be a promising approach to stop generalized spike‐and‐wave discharges (GSWDs) characteristic of absence seizures. Here, we investigated to what extent modulation of neuronal firing in cerebellar nuclei (CN), which are anatomically in an advantageous position to disrupt cortical oscillations through their innervation of a wide variety of thalamic nuclei, is effective in controlling absence seizures.MethodsTwo unrelated mouse models of generalized absence seizures were used: the natural mutant tottering, which is characterized by a missense mutation in Cacna1a, and inbred C3H/HeOuJ. While simultaneously recording single CN neuron activity and electrocorticogram in awake animals, we investigated to what extent pharmacologically increased or decreased CN neuron activity could modulate GSWD occurrence as well as short‐lasting, on‐demand CN stimulation could disrupt epileptic seizures.ResultsWe found that a subset of CN neurons show phase‐locked oscillatory firing during GSWDs and that manipulating this activity modulates GSWD occurrence. Inhibiting CN neuron action potential firing by local application of the γ‐aminobutyric acid type A (GABA‐A) agonist muscimol increased GSWD occurrence up to 37‐fold, whereas increasing the frequency and regularity of CN neuron firing with the use of GABA‐A antagonist gabazine decimated its occurrence. A single short‐lasting (30–300 milliseconds) optogenetic stimulation of CN neuron activity abruptly stopped GSWDs, even when applied unilaterally. Using a closed‐loop system, GSWDs were detected and stopped within 500 milliseconds.InterpretationCN neurons are potent modulators of pathological oscillations in thalamocortical network activity during absence seizures, and their potential therapeutic benefit for controlling other types of generalized epilepsies should be evaluated. Ann Neurol 2015;77:1027–1049

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Abstract-Log-domain or translinear filters are regarded as being a promising alternative in the area of low-voltage filter design. To date, most publications have reported on synthesis of translinear filters. Although synthesis is more powerful than analysis, it must go together with a generally applicable analysis method in the same domain. In this paper, a general currentmode analysis method is proposed. By using a current-mode approach, we stay close to the existing theory on static translinear circuits, which might be beneficial in developing a general, possibly more powerful synthesis method.

A class-AB four-quadrant current multiplier constituted by a class-AB current amplifier and a current splitter which can handle input signals in excess of ten times the bias current is presented. The proposed circuit operation is based on the exponential characteristic of BJTs or subthreshold MOSFETs. The multiplier is designed using the latter devices and achieves very low power consumption. Simulation results show that from a 0.65 V supply, the proposed circuit consumes 12.4 nW static power while less than 230 dB total harmonic distortion is achieved for an input modulation index up to 10.Introduction: Based on the well-known exponential characteristics of BJTs or weak inversion MOSFETs, four-quadrant current multiplier circuits have been designed from different principles, e.g. transconductor/ conveyor based [1] and translinear circuit based [2] current multipliers. Most of them are restricted to class-A operation that does not allow the input signals' swing to become higher than their bias currents.In this Letter, a fully class-AB four-quadrant analogue current multiplier is presented. The proposed multiplier is formed by a dual output current amplifier which is biased by controlled currents generated from a current splitter. Both the amplifier and splitter circuits can be realised from the same basic circuit block, called Sinh transconductor, which provides class-AB operation. Therefore, fully class-AB multiplication is obtained. Owing to the class-AB operation, the multiplier circuit can be designed to process high input signal amplitudes while its bias current can be kept low. Circuit simulation using a 0.13 mm model parameter shows that, for a 0.5 nA bias current, input currents with amplitudes of 5 nA can be applied to the circuit and good fourquadrant multiplication is performed.

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