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Technology Development Initiative – Paper of the Month – October 2022

A figure from this study

Image copyright – Science.

Dense functional and molecular readout of a circuit hub in sensory cortex

Published in Science.

Authors

Cameron Condylis, Abed Ghanbari, Nikita Manjrekar, Karina Bistrong, Shenqin Yao, Zizhen Yao, Thuc Nghi Nguyen, Hongkui Zeng, Bosiljka Tasic, and Jerry L. Chen

Paper presented by Dr. Atul Daiwile and selected by the NIDA TDI Paper of the Month Committee.

Background and Technological Advancement

The molecular signatures (e.g. gene expression profile) of cells in the brain are used to identify the cellular components of neuronal circuitry. To identify cell types involved in neuronal circuits associated with a specific behavior,  Dr. Chen’s lab from Boston University developed a platform designated “Comprehensive readout of activity and cell type markers (CRACK)”. The CRACK platform combines multi-area two photon calcium imaging microscopy with hybridization chain reaction–fluorescence in situ hybridization (HCR-FISH) to label and track mRNA. CRACK allows researchers to first observe the electrical firing of neurons in the brain of a live mouse during a behavioral task, and then track the expression of specific genes in slices of the animal’s brain, ultimately linking specific cells and their molecular signatures to particular behaviors. Now with CRACK, researchers can record activity of multiple neurons and precisely identify those neurons. Through simultaneous imaging across identified cell types, they were able to measure  functional connectivity between subpopulations of neurons for a behavioral task.


Condylis, Cameron; Ghanbari, Abed; Manjrekar, Nikita; Bistrong, Karina; Yao, Shenqin; Yao, Zizhen; Nguyen, Thuc Nghi; Zeng, Hongkui; Tasic, Bosiljka; Chen, Jerry L

Dense functional and molecular readout of a circuit hub in sensory cortex Journal Article

In: Science, vol. 375, no. 6576, pp. eabl5981, 2022, ISSN: 1095-9203.

Abstract | Links

@article{pmid34990233,
title = {Dense functional and molecular readout of a circuit hub in sensory cortex},
author = {Cameron Condylis and Abed Ghanbari and Nikita Manjrekar and Karina Bistrong and Shenqin Yao and Zizhen Yao and Thuc Nghi Nguyen and Hongkui Zeng and Bosiljka Tasic and Jerry L Chen},
url = {https://pubmed.ncbi.nlm.nih.gov/34990233/},
doi = {10.1126/science.abl5981},
issn = {1095-9203},
year = {2022},
date = {2022-01-01},
urldate = {2022-01-01},
journal = {Science},
volume = {375},
number = {6576},
pages = {eabl5981},
abstract = {Although single-cell transcriptomics of the neocortex has uncovered more than 300 putative cell types, whether this molecular classification predicts distinct functional roles is unclear. We combined two-photon calcium imaging with spatial transcriptomics to functionally and molecularly investigate cortical circuits. We characterized behavior-related responses across major neuronal subclasses in layers 2 or 3 of the primary somatosensory cortex as mice performed a tactile working memory task. We identified an excitatory intratelencephalic cell type, Baz1a, that exhibits high tactile feature selectivity. Baz1a neurons homeostatically maintain stimulus responsiveness during altered experience and show persistent enrichment of subsets of immediately early genes. Functional and anatomical connectivity reveals that Baz1a neurons residing in upper portions of layers 2 or 3 preferentially innervate somatostatin-expressing inhibitory neurons. This motif defines a circuit hub that orchestrates local sensory processing in superficial layers of the neocortex.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

Close

Although single-cell transcriptomics of the neocortex has uncovered more than 300 putative cell types, whether this molecular classification predicts distinct functional roles is unclear. We combined two-photon calcium imaging with spatial transcriptomics to functionally and molecularly investigate cortical circuits. We characterized behavior-related responses across major neuronal subclasses in layers 2 or 3 of the primary somatosensory cortex as mice performed a tactile working memory task. We identified an excitatory intratelencephalic cell type, Baz1a, that exhibits high tactile feature selectivity. Baz1a neurons homeostatically maintain stimulus responsiveness during altered experience and show persistent enrichment of subsets of immediately early genes. Functional and anatomical connectivity reveals that Baz1a neurons residing in upper portions of layers 2 or 3 preferentially innervate somatostatin-expressing inhibitory neurons. This motif defines a circuit hub that orchestrates local sensory processing in superficial layers of the neocortex.

Close

  • https://pubmed.ncbi.nlm.nih.gov/34990233/
  • doi:10.1126/science.abl5981

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