Kristian Lensjø

@klensj.bsky.social

Neuroscientist at the University of Oslo, part-time heavy metalist at Deseized

6/ The "brakes on plasticity" framing captured something real, but PNNs may be more informative as features of within-class PV specialization than as general plasticity regulators. Where a cell sits on this axis likely shapes how it participates in circuit dynamics.

5/ PNN-negative PV neurons look different — expressing neuropeptides and GABA-A subunits more typical of Sst interneurons. Similar across-class continua have been described transcriptomically for broad interneuron populations; the PNN gives us a physical handle on one within a class.

4/ PNN-positive PV neurons are the mature fast-spiking specialists: Kv3 channels, Grin2a (mature NMDA), Gabra1 (fast GABA-A), oxidative phosphorylation, gap junctions (Gjd2). The canonical basket-cell phenotype, molecularly.

pyDESeq2 (within animal, PV basket cells +PNN vs -PNN, 69 donors). volcano plot, p=0.001 cutoff, l2fc 0.5 indicated with vertical gray line. Genes included in xenium spatial panel indicated in red, non-xenium genes in blue. Genes of interest highlighted by name.

3/ We combined Xenium spatial transcriptomics with post-hoc WFA staining in adult mouse cortex. 378,349 cells, same-section PNN quantification. To extend beyond our 297-gene panel, we trained a classifier (AUC = 0.87) and projected onto Allen scRNA-seq: 34,326 PV neurons, genome-wide.

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1/ 97% of cortical PNNs are on PV interneurons. But PNN-positive and PNN-negative PV cells don't split into two groups — they sit at different ends of a transcriptional continuum of fast-spiking specialization. New preprint 🧵

Expansion microscopy image of perineuronal nets (unpublished).