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

Abstract

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: .

Autoreceptor control of serotonin dynamics

“…Surprisingly, it was quite easy to give adjustments for a small number of parameters (Table 5 ) that distinguish between fast, slow, and hybrid responses. First, we raised the of SERT from 250 to 433 and this lowered the steady-state value of eht from 60 nM to 39.8 nM consistent with the measurements in [ 60 ]. Note that the slope of the slow parts of the experimental curves (red dots) in Fig.…”

“…The distribution is broad with a range of 45 to 70 nM, a mean of 58.7 nM and a standard deviation of 4.3 nM. This distribution is similar to the distributions seen in the pre-frontal cortex of mice in the Hashemi Lab [ 60 ]. For no autoreceptors, the distribution is given by the pink bars in Fig.…”

“…A major change from our 2010 model is that the steady state eht concentration is now 60 nM instead of 0.7 nM. The Hashemi Lab has repeatedly verified that the extracellular serotonin concentration in mice is in the range 40–80 nM [ 60 – 62 ], although it varies considerably between the different regions to which the dorsal raphe and medial raphe project. The steady state concentration of histamine in the extracellular space is taken from [ 54 ].…”

“…We reported in prior work that a power analysis recommended a minimum n size of 3.5 (rounded to 4) and maintained that there, along with a strict animal exclusion criteria (i.e. animals that did not survive the experiment, animals in which the electrodes broke and animals in which the identity of the analyte could not be confirmed electrochemically via inspection of cyclic voltammograms [ 60 ].…”

Chronic SSRI treatment reverses HIV-1 protein-mediated synaptodendritic damage

“…Uptake 2 occurs as a result of non-SERT transporters and is characterized by higher 5 22 efficiency, but lower capacity and affinity. Studies in mice have shown that Uptake 2 has a much shorter decay curve that reaches baseline activity quickly(Abdalla et al, 2019). These studies 5 have further suggested that serotonin release in the hippocampus is largely mediated by Uptake5 2 (non-SERT) mechanisms (West et al, 2018; Abdalla et al, 2019).…”