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Abstract

Glutamate and γ-aminobutyric acid (GABA) are the most common neurotransmitters in the central nervous system, activating both ionotropic and metabotropic (modulatory) receptors. By exciting, inhibiting, and even modulating neural elements and microcircuits, these chemicals critically regulate brain information processing and energy metabolism at different spatiotemporal scales. Although a great deal of work has been done at the biophysical and cellular level, the exact relationship between the extracellular concentration of these molecules and emergence of specific patterns in neuronal ensemble activity remains elusive. Partly this is due to the fact that recording of the mean extracellular field potentials (mEFP) concurrently with a quantitative assessment of alterations in the concentration of such neurochemicals are currently unavailable. Here, we present a silicon-based implantable ultrafine microelectrode array (35 µm diameter and 50 µm thickness) composed of several iridium-stabilized electrochemical and electrophysiological contacts. The distance between each electrode channel is 250 µm. The electrophysiological electrodes have an average impedance of 0.5 MΩ at 1 kHz. The amperometric electrochemical channels are divided into two groups of glutamate- and GABA-responsive electrodes with the former showing a sensitivity of 0.39 nA µM−1 for glutamate, while the adjacent channel has a sensitivity of 0.38 nA µM−1 for GABA. Both have a detection limit of 0.2 µM. This novel multimodal microelectrode was used to simultaneously monitor extracellular glutamate and GABA concentrations, spikes, multi-unit neuronal activity (MUA) and local field potentials (LFP) in the lateral geniculate nucleus (LGN) of anaesthetized, adult Wistar rats (n=5). Retinal stimulation with flickering monochromatic light, emphasizing the simplest form of feedforward processing in thalamus, induced neuronal response patterns in LGN that were highly correlated with the temporal alterations in glutamate concentrations. GABA responses, while similar in profile to MUA and LFP recordings, were found to be event-selective and uncorrelated with the overall range of neuronal activity, suggesting the involvement of network processes that require further investigation. Our findings suggest that this multimodal method may greatly contribute into our understanding of microcircuit organization, by reducing the inherent ambiguity in the mEFP through neurotransmitter-release-tracking. Understanding microcircuits and their interactions is the only hope to develop neural networks models that my underly the brain’s function and dysfunction.