A computational study on synaptic and extrasynaptic effects of astrocyte glutamate uptake on orientation tuning in V1

TL;DR

This study uses computational modeling to explore how astrocyte glutamate uptake influences orientation tuning in V1, revealing that changes in glutamate levels modulate excitatory and inhibitory neuron contributions, affecting stimulus representation.

Contribution

It introduces a computational framework to analyze synaptic and extrasynaptic effects of glutamate uptake on neural tuning, linking pharmacological and genetic manipulations to network activity.

Findings

Glutamate uptake affects excitatory and inhibitory contributions to tuning.

Pharmacological blockade broadens tuning curves, enhances responses.

Genetic reduction of transporters sharpens tuning.

Abstract

Astrocytes affect neural transmission by a tight control via glutamate transporters on glutamate concentrations in direct vicinity to the synaptic cleft and by extracellular glutamate. Their relevance for information representation has been supported by in-vivo studies in ferret and mouse primary visual cortex. In ferret blocking glutamate transport pharmacologically broadened tuning curves and enhanced the response at preferred orientation. In knock-out mice with reduced expression of glutamate transporters sharpened tuning was observed. It is however unclear how focal and ambient changes in glutamate concentration affect stimulus representation. Here we develop a computational framework, which allows the investigation of synaptic and extrasynaptic effects of glutamate uptake on orientation tuning in recurrently connected network models with pinwheel-domain (ferret) or salt-and-pepper (mouse) organization. This model proposed that glutamate uptake shapes information representation when it affects the contribution of excitatory and inhibitory neurons to the network activity. Namely, strengthening the contribution of excitatory neurons generally broadens tuning and elevates the response. In contrast, strengthening the contribution of inhibitory neurons can have a sharpening effect on tuning. In addition local representational topology also plays a role: In the pinwheel-domain model effects were strongest within domains - regions where neighboring neurons share preferred orientations. Around pinwheels but also within salt-and-pepper networks the effects were less strong. Our model proposes that the pharmacological intervention in ferret increases the contribution of excitatory cells, while the reduced expression in mouse increases the contribution of inhibitory cells to network activity.