Local Chemical Gradients in a Mammalian Cortex Measured In Vivo With a Silicon Nanodialysis Mass Spectrometry...

Chemical extrasynaptic signaling in the mammalian brain is involved in the control of behavior via modulation of neural activity, in wiring the brain by directing the axonal growth, in localization of pharmacological effects of drugs, and in regulating the neuroinflammation. Local gradients of various neurochemicals in the brain are difficult to study in vivo due to their complex spatiotemporal dynamics induced by intricate interactions between neurons and glial cells that are not well understood. Here, to directly measure in vivo gradients of multiple neurotransmitters and metabolites simultaneously, we utilize an open-flow silicon nanodialysis sampling platform coupled with sensitive mass spectrometry. Results reveal strong millimeter-scale spatial gradients in concentration of neurotransmitters, neuromodulators, and astroglial modulators in a mouse cortex. Formation and maintenance of such local chemical compartments indicate strong regulation of brain neurochemistry by glial-neuron interactions that may heavily influence physiological and pathophysiological modulation of brain functions.