Low-Frequency Oscillations of In Vivo Ambient Extracellular Brain Serotonin

Abstract

Serotonin is an important neurotransmitter that plays a major role in many aspects of neuroscience. Fast-scan cyclic voltammetry measures fast in vivo serotonin dynamics using carbon fiber microelectrodes. More recently, fast-scan controlled-adsorption voltammetry (FSCAV) has been developed to measure slower, minute-to-minute changes in ambient extracellular serotonin. We have previously demonstrated that FSCAV measurements of basal serotonin levels give critical information regarding brain physiology and disease. In this work, we revealed the presence of low-periodicity fluctuations in serotonin levels in mouse hippocampi, measured in vivo with FSCAV. Using correlation analyses, we found robust evidence of oscillations in the basal serotonin levels, which had a period of 10 min and were not present in vitro. Under control conditions, the oscillations did not differ between male and female mice, nor do they differ between mice that underwent a chronic stress paradigm and those in the control group. After the acute administration of a selective serotonin reuptake inhibitor, we observed a shift in the frequency of the oscillations, leading us to hypothesize that the newly observed fluctuations were transporter regulated. Finally, we optimized the experimental parameters of the FSCAV to measure at a higher temporal resolution and found more pronounced shifts in the oscillation frequency, along with a decreased oscillation amplitude. We postulate that this work may serve as a potential bridge for studying serotonin/endocrine interactions that occur on the same time scale.

Keywords

• serotonin
• depression
• fluctuations
• serotonin transporter
• antidepressants