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Nonlinear photonic neuromorphic chips for spiking reinforcement learning

Photonic computing chips have made significant progress in accelerating linear computations, but nonlinear computations are usually implemented in the digital domain, which introduces additional system latency and power consumption, and hinders the implementation of fully functional photonic neural network chips. Here, we propose and fabricate a 16-channel programmable incoherent photonic neuromorphic computing chip by co-designing a simplified Mach–Zehnder interferometer (MZI) mesh and distributed feedback lasers with saturable absorber (DFBs-SA) array using different materials, enabling implementation of both linear and nonlinear spike computations in the optical domain through two separate chips. Furthermore, previous studies mainly focused on supervised learning and simple image classification tasks. Here, we propose a photonic spiking reinforcement learning (RL) architecture for the first, to our knowledge, time, and develop a software–hardware collaborative training-inference framework (in situ photonic training and hardware-aware fine-tuning) to address the challenge of training spiking RL models. We achieve large-scale, energy-efficient (photonic linear computation: 1.39 TOPS/W, photonic nonlinear computation: 987.65 GOPS/W), and low-latency (on-chip 320 ps) deployment of an entire layer of photonic spiking RL. Two RL benchmarks including the discrete CartPole task and the continuous Pendulum task are demonstrated experimentally based on the spiking proximal policy optimization (PPO) algorithm. The hardware–software collaborative computing reward value converges to 200 (−250) for the CartPole (Pendulum) tasks, respectively, comparable to that of a traditional PPO algorithm. This experimental demonstration addresses the challenge of the absence of large-scale on-chip photonic nonlinear spike computation and spiking RL training difficulty, and presents a high-speed and low-latency photonic spiking RL solution with promising application prospects in fields such as robot control, autonomous driving, and embodied intelligence.

Cancer drug reduces early Alzheimer’s-like brain hyperconnectivity in lab tests

Neuroscientists at King’s College London have pinpointed a mechanism behind the increased neural connectivity observed in the very early stages of Alzheimer’s disease. Published in Translational Psychiatry, the study also demonstrated that a cancer medication has the potential to reduce this hyperconnectivity.

The research showed that low levels of the protein amyloid-beta could induce hyperconnectivity and this pattern closely resembled changes seen in the brains of people with mild cognitive impairment (MCI). Amyloid-beta is thought to be instrumental in Alzheimer’s disease, where it creates plaques—or sticky clumps of amyloid-beta proteins—around the neurons.

These new findings suggest that low levels of amyloid-beta alone are enough to trigger early, disease-relevant changes in how brain cells connect.

Feedback control of random networks as a model of flexible motor cortical dynamics across tasks

Kalidindi and Crevecoeur develop a computational framework linking feedback-controlled networks to limb dynamics. They demonstrate that optimal control of fixed network reproduces key motor cortical dynamics and predicts neural activity across tasks. Analytical results show low-dimensional patterns emerge from task and biomechanical complexity, thereby bridging neural dynamics with control theory.

Mitochondrial complex-derived ROS induces lysosomal dysfunction and impairs autophagic flux in human cells carrying the APOE4 allele

The APOE4 allele is the strongest genetic risk factor for sporadic Alzheimer’s disease (sAD), yet its cell-autonomous effects remain poorly understood. While young, asymptomatic APOE4 carriers exhibit abnormal brain metabolism, the mechanistic link between mitochondrial dysfunction and lysosomal-autophagic failure remains unclear. In this study, we conducted a comprehensive analysis of primary human fibroblasts from APOE3 controls, APOE4, and sAD donors to assess mitochondrial bioenergetics, oxidative stress, autophagy, and lysosomal function. APOE4 fibroblasts displayed increased mitochondrial content-associated markers (PGC1α, mtDNA) accompanied by reduced respiratory capacity, elevated proton leak, and excessive mitochondrial ROS. In parallel, APOE4 fibroblasts showed impaired autophagic flux and reduced LC3-TOMM20 colocalization, indicating defective mitophagy. Lysosomal proteolytic activity, assessed using DQ-BSA, was significantly reduced and remained unresponsive under to starvation, in contrast to the partial recovery observed in sAD cells. Pharmacological targeting of mitochondrial ROS with site-specific inhibitors revealed that complex III-derived ROS is the predominant driver of redox stress in APOE4 fibroblasts, while complex I contributes primarily in sAD. Notably, selective inhibition of complex III-derived ROS with S3QEL restored lysosomal degradation, autophagic flux, and mitochondrial respiration in APOE4 cells. Together, these findings demonstrate that mitochondrial oxidative stress disrupts the mitochondria-lysosome axis in an APOE4-specific manner, revealing early and mechanistically distinct vulnerabilities that may precede neurodegeneration. Our results challenge the notion that APOE4 merely amplifies AD pathology and instead identity site-specific redox signaling as a promising target for allele-informed interventions.

Keywords: APOE4; Autophagy; Human fibroblasts; Lysosome; Mitochondria; Mitochondrial complex III; S3QEL.

Copyright © 2024. Published by Elsevier B.V.

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