Finally, in CA1 engram (Fos+) neurons, we found upregulated isoforms (Egr1-201, Junb-201, Arpc2-201) and downregulated isoforms (Plp1-201). Notably, Arpc2-201—a learning-linked cytoskeletal isoform—suggests structural remodeling during engram activation.

For example Baiap2; which encodes an abundant scaffolding protein (Irsp53) in the postsynaptic density. We observed no differential expression, only differential splicing, resulting in loss of the C-terminal PDZ binding motif, needed for postsynaptic density localization.

We generated single-cell long-read hippocampal data from 17 total mice subjected to one of three contextual experiences: Fear-conditioned (C+), Unconditioned (U+), or Naive (N). 20% of experience-variable isoforms arise from genes with no detectable difference at the gene level.

Using @10xgenomics.bsky.social Genomics and @nanoporetech.com sequencing, we generated the first single-cell long-read dataset of the mouse hippocampus. For example, S100a16, a calcium-binding protein, has cell-type alternative isoforms undetectable with standard 10X 3’ short-read data:

I think 5kb, 10kb, 25kb, 50kb and 100kb personally.