Thank you for attending the BICCN Flagship Release Webinar - Decoding the Mammalian Motor Cortex or viewing the recording on Youtube.
Below are the questions from our audience and the answers from our panelists. Please use this thread to ask additional questions or follow up on the conversation more generally.
Question: How practical is it to identify the major targets of a MOp cell from its gene expression profile?
Zhuzhu Xhang: In terms of the DNA methylation, some targets have more distinct profiles and others are more similar. Therefore, when we use selected DNA methylation features to predict the targets, the accuracy varies. From a separate study, we see that using gene expression profile works similarly in differentiating targets.
Hongkui Zeng: For GABAergic interneurons, we now have very good predictions o f axon projection patterns and layer specificity from the cell’s gene expression profile. For long-range projecting excitatory neurons, the picture is more complex. At cell subclass (major type) level, gene expression predicts overall projection patterns very well. This includes L2/3 IT, L4 IT, L5 IT, L6 IT, L5 ET medulla-projecting, L5 ET non-medulla-projecting, L6 CT, and L6b. Below this level, there is a lot of variability for individual cell’s projection patterns (how many targets, which targets, etc.) that can’t be precisely predicted by gene expression profile yet.
Question: How does this info translate into regenerative medicine, such as repairing damage in stroke or cerebral palsy? What needs to happen to get there from where we are now given this data?
Jump to panelists’ live discussion: Revealing the Mammalian Motor Cortex: BICCN Flagship Release - YouTube
Question: How would be single-cell spatial gene mapping related to macroscale PET and fMRI mappings?
Jump to panelists’ live discussion: Revealing the Mammalian Motor Cortex: BICCN Flagship Release - YouTube
Question: Is phenotype metadata available for the samples included in BICCN?
Carol Thompson: Metadata for raw data is on github, archives, and will go into Data Catalog; phenotype data is going into ontology & access through an online resource in coming months
Question: What is the computational challenges on this huge, complex, heterogeneous data collection? Thanks!
Jump to panelists’ live discussion: Revealing the Mammalian Motor Cortex: BICCN Flagship Release - YouTube
Question: Are there efforts to standardize morphological and EP features such that they could be combined with the transcriptomic/epigenomic features to produce unsupervised integrative cell type clustering and connectivity features?
Hongkui Zeng: Yes we are trying to collect this type of data, linking morphology and projection with transcriptomic profile at single cell level. BARseq is one example approach.
Question: why does the project aim at motor cortex? what will be the next target after then?
Jump to panelists’ live discussion: Revealing the Mammalian Motor Cortex: BICCN Flagship Release - YouTube
Question: Given the rich functional data from the primary motor cortex during movements, how can we go about mapping this genomic information to function in motor cortices such as during reaching tasks in mice?
Jump to panelists’ live discussion: Revealing the Mammalian Motor Cortex: BICCN Flagship Release - YouTube
Question: Thank you for this tremendous and beautiful collection of work! And the efforts to pool and share data and meta analyses. Beyond the utility for Neuroscientists though - is there a public engagement plan for explaining broader aspects of this impressive work? Showing its utility more broadly? There are so many misunderstandings of regional brain functionality in popular discussion. Cross modality alone is not well communicated in public arenas. BICCN seems well poised to wonderfully explain aspects of scale and connectivity, and clarify the progress of knowledge about circuits and regions in the mammalian brain. As in, providing a theoretical map for where we are now in the knowledge space : What do we know? What is left to know?
Jump to panelists’ live discussion Revealing the Mammalian Motor Cortex: BICCN Flagship Release - YouTube