Neural bistability and amplification mediated by NMDA receptors: Analysis of stationary equations

The macroscopic current/voltage relationship of NMDA receptor ion channels is nonmonotonic under physiological conditions, which can give rise to bistable and amplifying/facilitatory behavior in neurons and neural structures, supporting significant computational primitives. Conditions under which bistable regimes of operation prevail, and also general amplifying properties associated with active NMDA receptors, are examined in a single compartment enclosed by a cell membrane, and subsequently in cable-like dendrites under varying boundary conditions. Methodology consists of numerical and mathematical analyses of stationary versions of equations governing the electrical behavior of these systems. Bistability mediated by NMDA receptors requires interaction with other conductances in the membrane or cytoplasm, with particular importance attached to membrane potassium conductance, especially that of inward-rectifying potassium channels. A corollary conclusion is that coactivation of GABA B synaptic receptors or SK channels is a computationally powerful and sometimes necessary adjunct condition for NMDA receptor-mediated bistability. Neural multistability due to dendritic bistability is considered, including the case of closely coupled dendrites. The characteristics of coactivation-dependent facilitation, and amplifying states in which NMDA receptor activation boosts the efficacy of other classes of synapses, are also described. Coactive inward-rectifying potassium channels are found to significantly affect the characteristics of such amplification. ► Bistability and amplification may be mediated by NMDA receptors. ► Phenomena examined in single compartments and cable-like dendrites. ► Inward-rectifying potassium channels play significant role in bistable behavior. ► Dendrites may be independently bistable, and neurons multistable.