Jobe T, Vimal R, Kovilparambil A, Port J, Gaviria M
Neuropsychiatric Services, University of Illinois, Chicago 60612.
Neurol Res. 1994 Oct;16(5):330-41. doi: 10.1080/01616412.1994.11740250.
Recent research in computational neuroscience has suggested that psychosis associated with disturbed catecholamine neurotransmission may result from disturbances in the gain parameters of neural networks that these same secondary neurotransmitters are thought to control. We propose a mathematical model based upon cooperativity theory used in thermodynamics to explain how the gain parameter that momentarily increases the effect upon the post-synaptic cell of a given weighted connection from the presynaptic cell could be instantiated in the fluctuating electrical conductance of the dendrite of a neuron without requiring extensive ion transport or utilization of the ATP energy cycle. More specifically we propose that catecholamine neurotransmission serves to maintain the dendrite in a cooperative state with regard to changes in electrical conductance due to impulse traffic alone. In this way we supply the neuron with an activity driven gain parameter that not only increases volume of neuronal output at very low energy cost but that also upscales cooperative effects at the mechanico-chemical level of the dendrite to the network level itself. An important implication of this model is that two extreme states for dendritic electrical conductance will occur if cooperativity is lost at the level of catecholamine depletion or excess due to drug effects. These are the AND gate effect in which dendritic conductance is so low that the neuron requires extensive synaptic activity in order to output significantly. We correlate this state with negative symptoms in schizophrenia and psychomotor retardation in depression as well as the rigidity in Parkinsonism. The other extreme is represented by the OR gated dendrite in which conductance is so high that even noisy input to the dendrite will lead to significant nerve cell output. We correlate this condition with the positive symptoms of schizophrenia, the agitated features of psychotic depression and the tremors of Parkinsonism.
计算神经科学领域的最新研究表明，与儿茶酚胺神经传递紊乱相关的精神病，可能源于神经网络增益参数的紊乱，而这些次级神经递质被认为对神经网络具有控制作用。我们提出了一个基于热力学协同理论的数学模型，以解释在不依赖广泛的离子转运或ATP能量循环的情况下，给定加权连接从突触前细胞到突触后细胞的瞬时效应增益参数，如何在神经元树突的波动电导中得以体现。更具体地说，我们认为儿茶酚胺神经传递有助于使树突在仅因冲动传递导致的电导变化方面保持协同状态。通过这种方式，我们为神经元提供了一个由活动驱动的增益参数，该参数不仅能以极低的能量成本增加神经元输出量，还能将树突在机械化学层面的协同效应提升至网络层面本身。该模型的一个重要意义在于，如果由于药物作用导致儿茶酚胺耗竭或过量，在树突电导层面失去协同性，将会出现两种极端状态。一种是“与门”效应，即树突电导极低，以至于神经元需要大量的突触活动才能产生显著输出。我们将这种状态与精神分裂症的阴性症状、抑郁症的精神运动迟缓以及帕金森病的僵硬症状相关联。另一个极端则由“或门”型树突代表，其电导极高，以至于即使是树突的噪声输入也会导致神经细胞产生显著输出。我们将这种情况与精神分裂症的阳性症状、精神病性抑郁症的激越特征以及帕金森病的震颤相关联。
