Impact of Dopamine Alteration on Brain Wide Functional Connectivity at Cellular Resolution
Technical Report,15 Aug 2018,14 Aug 2019
The Regents of the University of California, San Francisco San Francisco United States
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Widespread neuroplasticity exists in the brain leading to adaptation or maladaptation. This project aims to understand how alteration of dopamine systems, which are profoundly affected in Parkinsons disease PD, affects brain-wide plasticity at cellular resolution, employingthe vertebrate model organism zebrafish. During the first year of this project, we have established transgenic animals that simultaneously express a reporter-tagged enzyme nitroreductase NTRfor chemogenetic ablation of dopamine neurons to mimic the loss of theseneurons in PDand GCAMP6s a genetically encoded calcium indicator for imaging neuronal activity dynamics. We have found that, in freely behaving larval zebrafish, chemogenetic ablation of DA neurons significantly reduced locomotor activity measured by total distancestravelled at the population level. However, at the level of individual animals, a clear correlation was not observed between the severity of total DA neuron loss and extent of locomotor impairment. Two possible interpretations of these findings are 1 the lack of correlations between DA neuron loss and locomotor impairment at individual levels is due to the engagement of other neural systems in locomotor behavioral modulation. 2 The lack of linear correlations between DA neuron loss and locomotor impairment at individual levels is due to individual differences in the ability to activate a compensatory brain plasticity machinery.
- Anatomy and Physiology