# Information Load from Neuromediator Diffusion to Extrasynaptic Space: The Interplay between the Injection Frequency and Clearance

## TL;DR

This paper studies how glutamate diffusion affects information transfer in the brain, showing that controlling glutamate spread improves synaptic communication up to a certain release frequency.

## Contribution

The study introduces convection into glutamate diffusion models and quantifies its impact on information transfer and excitotoxicity.

## Key findings

- Preventing glutamate spread increases information exchange up to 30–50 Hz release frequencies.
- Glutamate clearance is effective at low convection rates and remains constant at higher rates.
- Excess extrasynaptic glutamate leads to altered physiological effects and excitotoxicity.

## Abstract

We investigate how glutamate spillover affects information transfer by analyzing the mutual information between release and extrasynaptic locations. Through tetanic release simulations, we aim to quantify the efficiency of information transfer in the presence of excess glutamate. Our study seeks to offer insights into synaptic information processing and excitotoxicity.

In our study, we simulate the release of glutamate, a neurotransmitter, from the presynaptic cell by modeling the diffusion of glutamate into both synaptic and extrasynaptic space around the synapse. We have also incorporated a new factor into our model: convection. This factor represents the process by which the body clears glutamate from the synapse. Due to this process, the physiological mechanisms that typically prevent glutamate from spreading beyond the synapse are altered. This results in a different distribution of glutamate concentrations, with higher levels outside the synapse than inside it. The variety of biological effects that occur in response to this extrasynaptic glutamate highlights the importance of preventing neurotransmitters from spreading beyond the synapse. We aim to explain the physical reasons behind these biological effects, which are observed as excitotoxicity. Our results show that preventing the spread of glutamate outside the synapse increases the amount of information exchanged within the synapse and its surroundings for frequencies of glutamate release up to 30–50 Hz, followed by a decrease. Additionally, we find that the rate at which glutamate is cleared from the synapse is effective at relatively low levels (≤0.5 nm/μs in our calculation grid) and remains constant at higher levels.