MIND II/SOFT-FIB

Multi-modal electrode assessment of biological interaction and in vivo neurotransmitter dynamics in a disease model of depression

Summary

Currently the main experimental options to measure in vivo neurotransmitter release following deep brain stimulation (DBS) are dialysis or voltammetry. However, neither of the two methods is adapted to do chronic, longitudinal in vivo measurements investigating how DBS impacts the dynamics of neurotransmitter release in rodent models of disease. To facilitate a chronic and stable monitoring of neurotransmitter projections in brain, this project will use fibre photometry (FP), a more appropriate approach to answer our experimental questions. FP can be used to monitor fluorescent sensors associated with general or subtype selective neural activity in specific brain regions. In this method an optic fiber is used to deliver the excitation light and to absorb the emitted fluorescence, which is then passed on to the photo detector and then to the amplifier for further signals processing. Molecules of interest are tagged using genetically encoded fluorescent indicators (GEIs), and can be quantified via exciting the GEIs to a higher energy state and by absorbing the emitted fluorescence. Using multi-modal microelectrodes with hybrid (optical/ electrical) capabilities micro-engineered in-house, the project will investigate acute and chronic medial forebrain bundle DBS and its impact on neural activity, as well as changes in dopamine and glutamate levels in the corresponding brain regions, e.g. nucleus accumbens, pre-frontal cortex and the ventral tegmental area, in healthy and experimental models of depression. The biological interaction between the brain and the implanted device will be closely studied via post mortem examination of the brain tissue.

Research status

We were able to successfully establish Fiber Photometry (FP), state-of-the-art technique, in the rat model enabling simultaneous FP recordings, DBS stimulation, and behavioral testing. The new established protocols allowed to chronically  record in freely moving animals or during behavioral tasks, neurotransmitter transients (from dopamine and calcium sensors) under different mfb-DBS parameters in different key regions involved in Major Depressive Disorder (MDD). Ongoing work is also focused on the implementation of readouts from new sensors like glutamate, GABA and norepinephrine.