Competition for glutamate between NMDA and AMPA receptors prevents runaway synaptic dynamics

Abstract Homeostatic plasticity is an important guarantee for proper neural function. However, long term potentiation (LTP) was thought of as positive feedback in Hebbian plasticity. In this condition, synapse after potentiation is prone to be further potentiated. This can cause runaway dynamics of synapse and affect the stability of neural network. In order to prevent runaway synaptic dynamics, negative feedback is needed. Upon induction of LTP, the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors was increased in the postsynaptic density (PSD). Due to the competition for glutamate between AMPA receptors and N-Methyl-D-aspartic acid (NMDA) receptors, the number of opened NMDA receptor channels will reduce. Since the induction of LTP is NMDA receptors dependent, reduction of the number of activated NMDA receptors will increase the threshold of LTP induction. So the LTP of synapse itself can form a negative feedback to LTP induction. To test this hypothesis, a synaptic model with NMDA receptors and AMPA receptors coexisted was developed. When the number of AMPA receptors was increased in the PSD, the number of opened NMDA receptors was reduced though the same number of glutamate was released from presynaptic terminal. This will increase the threshold of further LTP induction and stability of synapse and neural network.