Patch-clamp recording requires direct accessibility of the cell membrane to patch pipettes and allows the investigation of ion channel properties and functions in specific cellular compartments.The cell body and relatively thick dendrites are the most accessible compartments of a neuron,due to their large diameters and therefore great membrane surface areas.However,axons are normally inaccessible to patch pipettes because of their thin structure;thus studies of axon physiology have long been hampered by the lack of axon recording methods.Recently,a new method of patchclamp recording has been developed,enabling direct and tight-seal recording from cortical axons.These recordings are performed at the enlarged structure（axonal bleb） formed at the cut end of an axon after slicing procedures.This method has facilitated studies of the mechanisms underlying the generation and propagation of the main output signal,the action potential,and led to the finding that cortical neurons communicate not only in action potential-mediated digital mode but also in membrane potential-dependent analog mode.
Motor development has been extensively studied in human infants and children, with several established scales for the evaluation of motor functions. However, the study of the neuronal mechanisms underlying human motor development is hampered by the lack of good animal models. The common marmoset （Callithrix jacchus）, a small New World monkey, has recently attracted much attention as a potential non- human primate model for understanding human physiology and diseases. However, little is known about its gross motor development. In the present study, we found that marmosets have a critical period for motor development in postnatal weeks 2 to 5, and acquire most of their motor skills by 8 weeks of age. We also developed methods to assess their motor functions, which will be useful for the evaluation of motor performance in marmoset models of human diseases. In addition, we found that marmosets exhibit a ＂head-to-tail＂ sequence of motor development similar to that found in humans, further supporting the notion that they provide a good animal model for studying the neuronal mechanisms underlying human motor development.
Abstract To date, we still lack disease-modifying thera- pies for Alzheimer＇s disease （AD）. Here, we report that long-term administration of benfotiamine improved the cognitive ability of patients with AD. Five patients with mild to moderate AD received oral benfotiamine （300 mg daily） over 18 months. All patients were examined by positron emission tomography with Pittsburgh compound B （PiB-PET） and exhibited positive imaging with β- amyloid deposition, and three received PiB-PET imaging at follow-up. The five patients exhibited cognitive improve- ment as assayed by the Mini-Mental Status Examination （MMSE） with an average increase of 3.2 points at month 18 of benfotiamine administration. The three patients who received follow-up PiB-PET had a 36.7% increase in the average standardized uptake value ratio in the brain com- pared with that in the first scan. Importantly, the MMSE scores of these three had an average increase of 3 points during the same period. Benfotiamine significantly improved the cognitive abilities of mild to moderate AD patients independently of brain amyloid accumulation. Ourstudy provides new insight to the development of disease- modifying therapy.
