Quantifying constraints determining independent activation on NMDA receptors mediated currents from evoked and spontaneous synaptic transmission at an individual synapse

TL;DR

This study uses mathematical simulations to explore the biophysical constraints affecting independent activation of NMDA receptor-mediated currents by evoked and spontaneous neurotransmitter releases at individual synapses.

Contribution

It introduces a computational model analyzing how synaptic size, geometry, and diffusion influence the independence of evoked and spontaneous neurotransmission.

Findings

Smaller synapses with cohesive cleft spaces show higher crosstalk between signals.

Larger synapses with central affinity and narrower fusion spaces promote independent activation.

Simulation results align with experimental data, guiding future research on synaptic transmission.

Abstract

A synapse acts on neural transmission through a chemical process called synapses fusion between pre-synaptic and post-synaptic terminals. Presynaptic terminals release neurotransmitters either in response to action potential or spontaneously independent of presynaptic activity. However, it is still unclear the mechanism of evoked and spontaneous neuro-transmission that activate on postsynaptic terminals. To address this question, we examined the possibility that spontaneous and evoked neurotransmissions using mathematical simulations. We aimed to address the biophysical constraints that may determine independent activation on N-methyl-D-asparate (NMDA) receptor mediated currents in response to evoked and spontaneous glutamate molecules releases. In order to identify the spatial relation between spontaneous and evoked glutamate release, we considered quantitative factors, such as size of synapses, inhomogeneity of diffusion mobility, geometry of synaptic cleft, and release rate of neurotransmitter. Simulation results showed that as a synaptic size is smaller and if the cleft space is more cohesive in the peripheral area than the centre area, then there is high possibility of having crosstalk of two signals released from center and edge. When a synaptic size is larger, the cleft space is more affinity in the central area than the external area, and if the geometry of fusion has a narrower space, then those produce more chances of independence of two modes of currents released from center and edge. The computed results match well with existing experimental findings and serve as a road map for further exploration to identify independence of evoked and spontaneous releases.