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Multineuromodulator measurements across fronto-striatal network areas of the behaving macaque using solid-phase microextraction

Hassani, Seyed-Alireza
Lendor, Sofia
Boyacı, Ezel
Pawliszyn, Janusz
Womelsdorf, Thilo
Different neuromodulators rarely act independent from each other to modify neural processes but are instead coreleased, 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, multineuromodulator 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 covariation of neuromodulators during goal-directed behavior. Such data would be important to better distinguish between different behavioral states and characterize dysfunctional brain states that may be evident in psychiatric disorders.