A theory of cooperativity modulation in neural networks as an important parameter of CNS catecholamine function and induction of psychopathology.

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.