PT  - JOURNAL ARTICLE
AU  - Seyed-Alireza Hassani
AU  - Sofia Lendor
AU  - Ezel Boyaci
AU  - Janusz Pawliszyn
AU  - Thilo Womelsdorf
TI  - Multi-Neuromodulator Measurements across Fronto-Striatal Network Areas of the Behaving Macaque using Solid-Phase Microextraction
AID  - 10.1101/534651
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 534651
4099  - http://biorxiv.org/content/early/2019/08/02/534651.short
4100  - http://biorxiv.org/content/early/2019/08/02/534651.full
AB  - Different neuromodulators rarely act independent from each other to modify neural processes but are instead co-released, gated, or modulated. To understand this interdependence of neuromodulators and their collective influence on local circuits during different brain states, it is necessary to reliably extract local concentrations of multiple neuromodulators in vivo. Here we describe results using solid phase microextraction (SPME), a method providing sensitive, multi-neuromodulator measurements. SPME is a sampling method that is coupled with mass spectrometry to quantify collected analytes. Reliable measurements of glutamate, dopamine, acetylcholine and choline were made simultaneously within frontal cortex and striatum of two macaque monkeys (Macaca mulatta) during goal-directed behavior. We find glutamate concentrations several orders of magnitude higher than acetylcholine and dopamine in all brain regions. Dopamine was reliably detected in the striatum at tenfold higher concentrations than acetylcholine. Acetylcholine and choline concentrations were detected with high consistency across brain areas, within monkeys and between monkeys. These findings illustrate that SPME microprobes provide a versatile novel tool to characterize multiple neuromodulators across different brain areas in vivo to understand the interdependence and co-variation of neuromodulators during goal directed behavior. Such data will be important to better distinguish between different behavioral states and characterize dysfunctional brain states that may be evident in psychiatric disorders.New and Noteworthy Our manuscript reports a reliable and sensitive novel method for measuring the absolute concentrations of glutamate, acetylcholine, choline, dopamine and serotonin in brain circuits in-vivo. We show that this method reliably samples multiple neurochemicals in three brain areas simultaneously while nonhuman primates are engaged in goal directed behavior. We further describe how the methodology we describe here may be used by electrophysiologists as a low barrier to entry tool for measuring multiple neurochemicals.