Establishing In-vivo brain microdialysis for comparing concentrations of a variety of cortical neurotransmitters in the awake rhesus macaque between different cognitive states.

Abstract

Background: Neuronal activity is modulated by behavior and cognitive processes. The combination of several neurotransmitter systems, acting directly or indirectly on specific populations of neurons, underlie such modulations. Most studies with non-human primates (NHPs) fail to capture this complexity, partly due to the lack of adequate methods for reliably and simultaneously measuring a broad spectrum of neurotransmitters while the animal engages in behavioral tasks.

New method: To address this gap, we introduce a novel implementation of brain microdialysis (MD), employing semi-chronically implanted guides and probes in awake, behaving NHPs facilitated by removable insets within a standard recording chamber over extrastriate visual cortex (here, the visual middle temporal area (MT)). This approach allows flexible access to diverse brain regions, including areas deep within the sulcus.

Results: Reliable concentration measurements of GABA, glutamate, norepinephrine, epinephrine, dopamine, serotonin, and choline were achieved from small sample volumes (<20 µl) using ultra-performance liquid chromatography with electrospray ionization-mass spectrometry (UPLC-ESI-MS). Comparing two behavioral states - 'active' and 'inactive', we observe subtle concentration variations between the two behavioral states and a greater variability of concentrations in the active state. Additionally, we find positively and negatively correlated concentration changes for neurotransmitter pairs between the behavioral states.

Conclusions: Therefore, this MD setup allows insights into the neurochemical dynamics in awake primates, facilitating comprehensive investigations into the roles and the complex interplay of neurotransmitters in cognitive and behavioral functions.