Biohybrid restoration of the hippocampal loop re-establishes the non-seizing state in anin vitromodel of limbic seizures.

Objective. The compromise of the hippocampal loop is a hallmark of mesial temporal lobe epilepsy (MTLE), the most frequent epileptic syndrome in the adult population and the most often refractory to medical therapy. Hippocampal sclerosis is found in >50% of drug-refractory MTLE patients and primarily involves the CA1, consequently disrupting the hippocampal output to the entorhinal cortex (EC). Closed-loop deep brain stimulation is the latest frontier to improve drug-refractory MTLE; however, current approaches do not restore the functional connectivity of the hippocampal loop, they are designed by trial-and-error and heavily rely on seizure detection or prediction algorithms. The objective of this study is to evaluate the anti-ictogenic efficacy and robustness of an artificial bridge restoring the dialog between hippocampus and EC.Approach. In mouse hippocampus-EC slices treated with 4-aminopyridine and in which the Schaffer Collaterals are severed, we established an artificial bridge between hippocampus and EC wherein interictal discharges originating in the CA3 triggered stimulation of the subiculum so to entrain EC networks. Combining quantification of ictal activity with tools from information theory, we addressed the efficacy of the bridge in controlling ictogenesis and in restoring the functional connectivity of the hippocampal loop.Main results. The bridge significantly decreased or even prevented ictal activity and proved robust to failure; when operating at 100% of its efficiency (i.e., delivering a pulse upon each interictal event), it recovered the functional connectivity of the hippocampal loop to a degree similar to what measured in the intact circuitry. The efficacy and robustness of the bridge stem in mirroring the adaptive properties of the CA3, which acts as biological neuromodulator.Significance. This work is the first stepping stone toward a paradigm shift in the conceptual design of stimulation devices for epilepsy treatment, from function control to functional restoration of the salient brain circuits.

A CMOS-memristor hybrid system for implementing stochastic binary spike timing-dependent plasticity.

This paper describes a fully experimental hybrid system in which a [Formula: see text] memristive crossbar spiking neural network (SNN) was assembled using custom high-resistance state memristors with analogue CMOS neurons fabricated in 180 nm CMOS technology. The custom memristors used NMOS selector transistors, made available on a second 180 nm CMOS chip. One drawback is that memristors operate with currents in the micro-amperes range, while analogue CMOS neurons may need to operate with currents in the pico-amperes range. One possible solution was to use a compact circuit to scale the memristor-domain currents down to the analogue CMOS neuron domain currents by at least 5-6 orders of magnitude. Here, we proposed using an on-chip compact current splitter circuit based on MOS ladders to aggressively attenuate the currents by over 5 orders of magnitude. This circuit was added before each neuron. This paper describes the proper experimental operation of an SNN circuit using a [Formula: see text] 1T1R synaptic crossbar together with four post-synaptic CMOS circuits, each with a 5-decade current attenuator and an integrate-and-fire neuron. It also demonstrates one-shot winner-takes-all training and stochastic binary spike-timing-dependent-plasticity learning using this small system. This article is part of the theme issue 'Advanced neurotechnologies: translating innovation for health and well-being'.