This paper aims at exploring computational properties of dynamic processes in neu-ral systems,studying their mathematical formulation,and applying the results to artificial neuralnetwork modeling.The stimulus-response...This paper aims at exploring computational properties of dynamic processes in neu-ral systems,studying their mathematical formulation,and applying the results to artificial neuralnetwork modeling.The stimulus-response processes in neurons are first introduced briefly,thenproperties of neurons described by the Hodgkin-Huxley equations are analyzed.After studyinghow to simplify,the Hodgkin-Huxley equations while maintaining its properties,the concept of dy-namic neuron model is proposed.It is pointed out that the neuron model should include internalstates in order to obtain time-variant thresholds,such as refractory periods of neurons.Finallywe discuss problems related to neural network models based on pulse-stream communication andthe contribution of intraneuronal dynamics to collective properties of the neural network.展开更多
Beta amyloid (Aβ42)-induced dysfunction and loss of synapses are believed to be major underlying mechanisms for the progressive loss of learning and memory abilities in Alzheimer's disease (AD). The vast majorit...Beta amyloid (Aβ42)-induced dysfunction and loss of synapses are believed to be major underlying mechanisms for the progressive loss of learning and memory abilities in Alzheimer's disease (AD). The vast majority of investigations on AD-related synaptic impairment focus on synaptic plasticity, especially the decline of long-term potentiation of synaptic transmission caused by extracellular Aβ42. Changes in other aspects of synaptic and neuronal functions are less studied or undiscovered. Here, we report that intraneuronal accumulation of Aβ42 induced an age- dependent slowing of neuronal transmission along pathways involving multiple synapses.展开更多
The current idea behind brain pathology is that disease is initiated by mild disturbances of common physiological processes. Overtime, the disruption of the neuronal homeostasis will determine irreversible degeneratio...The current idea behind brain pathology is that disease is initiated by mild disturbances of common physiological processes. Overtime, the disruption of the neuronal homeostasis will determine irreversible degeneration and neuronal apoptosis. This could be also true in the case of nerve growth factor (NGF) al- terations in sporadic Alzheimer's disease (AD), an age-related pathology characterized by cholinergic loss, amyloid plaques and neurofibrillary tangles. In fact, the pathway activated by NGF, a key neurotrophin for the metabolism of basal forebrain cholinergic neurons (BFCN), is one of the first homeostatic systems affected in prodromal AD. NGF signaling dysfunctions have been thought for decades to occur in AD late stages, as a mere consequence of amyloid-driven disruption of the retrograde axonal transport of neuro- trophins to BFCN. Nowadays, a wealth of knowledge is potentially opening a new scenario: NGF signaling impairment occurs at the onset of AD and correlates better than amyloid load with cognitive decline. The recent acceleration in the characterization of anatomical, functional and molecular profiles of early AD is aimed at maximizing the efficacy of existing treatments and setting novel therapies. Accordingly, the elucidation of the molecular events underlying APP metabolism regulation by the NGF pathway in the sep- to-hippocampal system is crucial for the identification of new target molecules to slow and eventually halt mild cognitive impairment (MCI) and its progression toward AD.展开更多
In addition to senile plaques and cerebral amyloid angiopathy,the hyperphosphorylation of tau protein and formation of intraneuronal neurofibrillary tangles(NFTs)represents another neuropathological hallmark in AD bra...In addition to senile plaques and cerebral amyloid angiopathy,the hyperphosphorylation of tau protein and formation of intraneuronal neurofibrillary tangles(NFTs)represents another neuropathological hallmark in AD brain.Tau is a microtubule-associated protein and localizes predominantly in the axons of neurons with the primary function in maintaining microtubules stability.When the balance between tau phosphorylation and dephosphorylation is changed in favor of the former,tau is hyperphosphorylated and the level of the free tau fractions elevated.The hyperphosphorylation of tau protein and formation of NFTs represent a characteristic neuropathological feature in AD brain.We have discussed the role of Aβin AD in our previous review,this review focused on the recent advances in tau-mediated AD pathology,mainly including tau hyperphosphorylation,propagation of tau pathology and the relationship between tau and Aβ.展开更多
文摘This paper aims at exploring computational properties of dynamic processes in neu-ral systems,studying their mathematical formulation,and applying the results to artificial neuralnetwork modeling.The stimulus-response processes in neurons are first introduced briefly,thenproperties of neurons described by the Hodgkin-Huxley equations are analyzed.After studyinghow to simplify,the Hodgkin-Huxley equations while maintaining its properties,the concept of dy-namic neuron model is proposed.It is pointed out that the neuron model should include internalstates in order to obtain time-variant thresholds,such as refractory periods of neurons.Finallywe discuss problems related to neural network models based on pulse-stream communication andthe contribution of intraneuronal dynamics to collective properties of the neural network.
基金supported by the National Natural Science Foundation of China(81071026 and 81371400)the National Basic Research Development Program of China(2013CB530900)
文摘Beta amyloid (Aβ42)-induced dysfunction and loss of synapses are believed to be major underlying mechanisms for the progressive loss of learning and memory abilities in Alzheimer's disease (AD). The vast majority of investigations on AD-related synaptic impairment focus on synaptic plasticity, especially the decline of long-term potentiation of synaptic transmission caused by extracellular Aβ42. Changes in other aspects of synaptic and neuronal functions are less studied or undiscovered. Here, we report that intraneuronal accumulation of Aβ42 induced an age- dependent slowing of neuronal transmission along pathways involving multiple synapses.
基金supported by Ministry of Education,Universities and Research(MIUR/FIRB)funding to PC
文摘The current idea behind brain pathology is that disease is initiated by mild disturbances of common physiological processes. Overtime, the disruption of the neuronal homeostasis will determine irreversible degeneration and neuronal apoptosis. This could be also true in the case of nerve growth factor (NGF) al- terations in sporadic Alzheimer's disease (AD), an age-related pathology characterized by cholinergic loss, amyloid plaques and neurofibrillary tangles. In fact, the pathway activated by NGF, a key neurotrophin for the metabolism of basal forebrain cholinergic neurons (BFCN), is one of the first homeostatic systems affected in prodromal AD. NGF signaling dysfunctions have been thought for decades to occur in AD late stages, as a mere consequence of amyloid-driven disruption of the retrograde axonal transport of neuro- trophins to BFCN. Nowadays, a wealth of knowledge is potentially opening a new scenario: NGF signaling impairment occurs at the onset of AD and correlates better than amyloid load with cognitive decline. The recent acceleration in the characterization of anatomical, functional and molecular profiles of early AD is aimed at maximizing the efficacy of existing treatments and setting novel therapies. Accordingly, the elucidation of the molecular events underlying APP metabolism regulation by the NGF pathway in the sep- to-hippocampal system is crucial for the identification of new target molecules to slow and eventually halt mild cognitive impairment (MCI) and its progression toward AD.
基金This work was supported by the grants from the National Natural Science Foundation of China(No.31171019,No.81173108,No.31000574 and No.31200820)the Opening Projects of Shanghai Key Laboratory of Brain Functional Genomics and Key Laboratory of Brain Functional Genomics(East China Normal University),Ministry of Education。
文摘In addition to senile plaques and cerebral amyloid angiopathy,the hyperphosphorylation of tau protein and formation of intraneuronal neurofibrillary tangles(NFTs)represents another neuropathological hallmark in AD brain.Tau is a microtubule-associated protein and localizes predominantly in the axons of neurons with the primary function in maintaining microtubules stability.When the balance between tau phosphorylation and dephosphorylation is changed in favor of the former,tau is hyperphosphorylated and the level of the free tau fractions elevated.The hyperphosphorylation of tau protein and formation of NFTs represent a characteristic neuropathological feature in AD brain.We have discussed the role of Aβin AD in our previous review,this review focused on the recent advances in tau-mediated AD pathology,mainly including tau hyperphosphorylation,propagation of tau pathology and the relationship between tau and Aβ.