NIDA IRP Technology Development Initiative Featured Paper

Image copyright – eNeuro.

SMART: An Open-Source Extension of WholeBrain for Intact Mouse Brain Registration and Segmentation

Published in eNeuro.

Authors

Michelle Jin, Joseph D Nguyen, Sophia J Weber, Carlos A Mejias-Aponte, Rajtarun Madangopal, Sam A Golden

Paper presented by Dr. Katherine Savell and selected by the NIDA TDI Paper of the Month Committee.

Background and Technological Advancement

Whole-brain activity mapping provides one way to understand which brain regions encode and control behavior and cognition. However, achieving consistent staining conditions in three-dimensional tissue and analysis of the resulting large datasets remain a challenge. Jin et al. present an optimized protocol for Fos staining, a marker of neuronal activation, in a cleared mouse brain and provide an open-source R package called SMART (Semi-Manual Alignment to Reference Templates) as an extension to the Wholebrain pipeline (PMID: 29203898). SMART is designed to make whole-brain activity mapping more accessible to researchers looking to implement the technique and analysis into their research program.

Jin, Michelle; Nguyen, Joseph D; Weber, Sophia J; Mejias-Aponte, Carlos A; Madangopal, Rajtarun; Golden, Sam A

SMART: An Open-Source Extension of WholeBrain for Intact Mouse Brain Registration and Segmentation Journal Article

In: eNeuro, vol. 9, no. 3, 2022, ISSN: 2373-2822.

Abstract | Links

@article{pmid35396258,

title = {SMART: An Open-Source Extension of WholeBrain for Intact Mouse Brain Registration and Segmentation},

author = {Michelle Jin and Joseph D Nguyen and Sophia J Weber and Carlos A Mejias-Aponte and Rajtarun Madangopal and Sam A Golden},

url = {https://pubmed.ncbi.nlm.nih.gov/35396258/},

doi = {10.1523/ENEURO.0482-21.2022},

issn = {2373-2822},

year  = {2022},

date = {2022-05-03},

journal = {eNeuro},

volume = {9},

number = {3},

abstract = {Mapping immediate early gene (IEG) expression across intact mouse brains allows for unbiased identification of brain-wide activity patterns underlying complex behaviors. Accurate registration of sample brains to a common anatomic reference is critical for precise assignment of IEG-positive ("active") neurons to known brain regions of interest (ROIs). While existing automated voxel-based registration methods provide a high-throughput solution, they require substantial computing power, can be difficult to implement and fail when brains are damaged or only partially imaged. Additionally, it is challenging to cross-validate these approaches or compare them to any preexisting literature based on serial coronal sectioning. Here, we present the open-source R package SMART (Semi-Manual Alignment to Reference Templates) that extends the WholeBrain R package framework to automated segmentation and semi-automated registration of intact mouse brain light-sheet fluorescence microscopy (LSFM) datasets. The SMART package was created for novice programmers and introduces a streamlined pipeline for aligning, registering, and segmenting LSFM volumetric datasets across the anterior-posterior (AP) axis, using a simple "choice game" and interactive menus. SMART provides the flexibility to register whole brains, partial brains or discrete user-chosen images, and is fully compatible with traditional sectioned coronal slice-based analyses. We demonstrate SMART's core functions using example datasets and provide step-by-step video tutorials for installation and implementation of the package. We also present a modified iDISCO+ tissue clearing procedure for uniform immunohistochemical labeling of the activity marker Fos across intact mouse brains. The SMART pipeline, in conjunction with the modified iDISCO+ Fos procedure, is ideally suited for examination and orthogonal cross-validation of brain-wide neuronal activation datasets.},

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pubstate = {published},

tppubtype = {article}

}