Impact of Dopamine Alteration on Brain-Wide Functional Connectivity at Cellular Resolution

Abstract

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 Parkinson's disease (PD), affects brain-wide plasticity at cellular resolution, employing the vertebrate model organism zebrafish. Zebrafish offers unique strength for brain-wide imaging and high throughput capability for screening. In this study, we harvest these strengths to understand brain plasticity and identify potentially therapeutic agents for treating PD. Using transgenic animals that express a reporter-tagged enzyme nitroreductase (NTR), we chemogenetically ablated dopamine neurons to mimic the loss of these neurons in PD. Using this model, we have uncovered brain-wide mechanisms (at both activity and connectivity levels) that serve to compensate for the loss of DA neurons. We have also performed a small molecule screen that uncovered potential therapeutics for treating PD.

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Document Details

Document Type
Technical Report
Publication Date
Dec 01, 2021
Accession Number
AD1204129

Entities

People

  • Su Guo

Organizations

  • University of California Regents

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Blood-Brain Barrier
  • Brain
  • Chemical Compounds
  • Chemical Synthesis
  • Chemistry
  • Confocal Microscopy
  • Databases
  • Fish
  • Genetically Modified Organisms
  • Genetics
  • Health Services
  • Medical Personnel
  • Molecular Biology
  • Neurodegeneration
  • Neurons
  • Neurosciences
  • Parkinson'S Disease
  • Proteins
  • Small Molecules

Fields of Study

  • Biology

Readers

  • Neurodegenerative Parkinson's Disease and Rickettsial Disease handbook, including the data level of dopamine, BC, neurons, and PD.
  • Neuroscience