학술논문

Deep learning-based image analysis identifies a DAT-negative subpopulation of dopaminergic neurons in the lateral Substantia nigra.
Document Type
Article
Source
Communications Biology. 11/10/2023, Vol. 6 Issue 1, p1-26. 26p.
Subject
*DEEP learning
*SUBSTANTIA nigra
*DOPAMINERGIC neurons
*IMAGE analysis
*ALDEHYDE dehydrogenase
*TYROSINE hydroxylase
*PARKINSON'S disease
Language
ISSN
2399-3642
Abstract
Here we present a deep learning-based image analysis platform (DLAP), tailored to autonomously quantify cell numbers, and fluorescence signals within cellular compartments, derived from RNAscope or immunohistochemistry. We utilised DLAP to analyse subtypes of tyrosine hydroxylase (TH)-positive dopaminergic midbrain neurons in mouse and human brain-sections. These neurons modulate complex behaviour, and are differentially affected in Parkinson's and other diseases. DLAP allows the analysis of large cell numbers, and facilitates the identification of small cellular subpopulations. Using DLAP, we identified a small subpopulation of TH-positive neurons (~5%), mainly located in the very lateral Substantia nigra (SN), that was immunofluorescence-negative for the plasmalemmal dopamine transporter (DAT), with ~40% smaller cell bodies. These neurons were negative for aldehyde dehydrogenase 1A1, with a lower co-expression rate for dopamine-D2-autoreceptors, but a ~7-fold higher likelihood of calbindin-d28k co-expression (~70%). These results have important implications, as DAT is crucial for dopamine signalling, and is commonly used as a marker for dopaminergic SN neurons. A deep learning-based image analysis platform quantifies cell numbers and mRNA or protein derived fluorescence signals, and is used to identify a unique population of dopamine transporter-negative dopaminergic neurons in the lateral Substantia nigra. [ABSTRACT FROM AUTHOR]