Long-standing methodological restrictions can be addressed by new technologies, such as fiber photometry, to further our knowledge of neural systems. The purpose of this work was to combine the innovative imaging approach with the recently developed dopamine indicator (GRABDA2m). Here, we provide proof-of-concept data and a comprehensive methodological road map for longitudinal repeated transmitter release tracking in in vivo freely moving animals. This innovative method allows for a new perspective on the Medial Forebrain Bundle (mfb) DBS-induced changes in dopamine release patterns in the nucleus accumbens in rodents. Our findings point to trustworthy dopamine level readouts across a minimum of 14 days of DBS-induced photometric observations. We demonstrate that mfb-DBS can induce a greater dopamine response after stimulation (5 s and 20 s DBS) in comparison to its pre-stimulus dopamine activity state, reaching its maximal amplitude in around 1 s before recovering. Future research would need to confirm the potential differential influence on this neurotransmitter response that is suggested by the effect of varied DBS Pulse Widths (PWs). With the method described, we hope to learn more about the distinctions between pathological and healthy models and to more thoroughly explain the mechanisms by which DBS exerts its therapeutic effect.
