Title: Tonic activation of extrasynaptic NMDA receptors decreases intrinsic excitability and promotes bistability in a model of neuronal activity,
Abstract: NMDA receptors (NMDA-R) typically contribute to excitatory synaptic
transmission in the central nervous system. While calcium influx through NMDA-R
plays a critical role in synaptic plasticity, indirect experimental evidence
also exists demonstrating actions of NMDAR-mediated calcium influx on neuronal
excitability through the activation of calcium-activated potassium channels.
But, so far, this mechanism has not been studied theoretically. Our theoretical
model provide a simple description of neuronal electrical activity including
the tonic activity of NMDA receptors and a cytosolic calcium compartment. We
show that calcium influx through NMDA-R can directly be coupled to activation
of calcium-activated potassium channels providing an overall inhibitory effect
on neuronal excitability. Furthermore, the presence of tonic NMDA-R activity
promotes bistability in electrical activity by dramatically increasing the
stimulus interval where both a stable steady state and repetitive firing can
exist. This results could provide an intrinsic mechanism for the constitution
of memory traces in neuronal circuits. They also shed light on the way by which
beta-amyloids can decrease neuronal activity when interfering with NMDA-R in
Alzheimer's disease.