Fast serotonin voltammetry as a versatile tool for mapping dynamic tissue architecture: I. Responses at carbon fibers describe local tissue physiology

• Published in: Journal of neurochemistry 2020-04, Vol.153 (1), p.33-50
• Main Authors: Abdalla, Aya, West, Alyssa, Jin, Yunju, Saylor, Rachel A., Qiang, Beidi, Peña, Edsel, Linden, David J., Nijhout, H. Frederik, Reed, Michael C., Best, Janet, Hashemi, Parastoo
• Format: Article
• Language: English
• Subjects: Animals; Axons - physiology; Brain; Brain - physiopathology; Brain Chemistry - physiology; Carbon; Carbon Fiber; Carbon fibers; confocal microscopy; Electric Stimulation; Electrochemical Techniques - methods; Evoked Potentials; FSCV; Heterogeneity; hippocampus; Hippocampus - chemistry; In vivo methods and tests; Male; Mapping; Medial Forebrain Bundle; Mental disorders; Mental Disorders - physiopathology; Mice; Mice, Inbred C57BL; Microelectrodes; Models, Theoretical; Neuroimaging; Physiology; Prefrontal cortex; Prefrontal Cortex - chemistry; Serotonin; Serotonin - analysis; Serotonin - metabolism; Stimulation; Substantia nigra; Substantia Nigra - chemistry; Substantia nigra pars reticulata; Tissues; Voltammetry
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/jnc.14854

It is important to monitor serotonin neurochemistry in the context of brain disorders. Specifically, a better understanding of biophysical alterations and associated biochemical functionality within subregions of the brain will enable better of understanding of diseases such as depression. Fast voltammetric tools at carbon fiber microelectrodes provide an opportunity to make direct evoked and ambient serotonin measurements in vivo in mice. In this study, we characterize novel stimulation and measurement circuitries for serotonin analyses in brain regions relevant to psychiatric disease. Evoked and ambient serotonin in these brain areas, the CA2 region of the hippocampus and the medial prefrontal cortex, are compared to ambient and evoked serotonin in the substantia nigra pars reticulata, an area well established previously for serotonin measurements with fast voltammetry. Stimulation of a common axonal location evoked serotonin in all three brain regions. Differences are observed in the serotonin release and reuptake profiles between these three brain areas which we hypothesize to arise from tissue physiology heterogeneity around the carbon fiber microelectrodes. We validate this hypothesis mathematically and via confocal imaging. We thereby show that fast voltammetric methods can provide accurate information about local physiology and highlight implications for chemical mapping. Cover Image for this issue: doi: 10.1111/jnc.14739. To demonstrate that chemical responses at carbon fiber microelectrodes can give information about local tissue physiology, we characterize novel medial forebrain bundle (MFB) stimulation and measurement circuitries for serotonin in the hippocampus (CA2), the medial prefrontal cortex (mPFC), and the substantia nigra (SNr). Differences are observed in serotonin chemistry which we show experimentally, mathematically and via imaging, to be indicative of tissue heterogeneity. This finding has important implications for chemical mapping. Open Science: This manuscript was awarded with the Open Materials Badge For more information see: https://cos.io/our-services/open-science-badges/ Cover Image for this issue: doi: 10.1111/jnc.14739.