We report co-occurring dendrite loss and sensory integration (visual mismatch responses) specific to supragranular (layer 2/3) neurons in visual cortex due to a missense mutation affecting Kalirin (KalPT) -- and specifically, the kal9 isoform.
This occurred against a backdrop of normal feature selectivity and firing rates in V1, as well as unaffected dendritic structure in other layers of V1.
Huge congrats to my grad student, Dr. Anna Rader Groves, who successfully defended her disseratation last week! I consider myself lucky to have mentored Anna over the past 5 years.
Both dendrite loss and reduced mismatch negativity are pronounced in numerous neuropsychiatric disorders. Correlating these observations in patient samples only gets us so far. Animal models provide a controlled system to understand how distinct features causally connect.
Anna joined my lab at the peak of covid, but quickly gathered data, coauthored key publications, and wrote a book chapter. On her first F31 submission, she scored a 2nd percentile (which was subsequently awarded).
Excited to share our preprint! Impressive effort from grad student Anna Rader Groves and co-author @cgalli-io.bsky.social, in collaboration with Melanie Grubisha and Robert Sweet (PITT). @grubisha
Although this particular variant may only explain a fraction of human pathologogy, its downstream impacts on neuronal structure via RhoA-GEF make it a useful system for connecting convergent molecular, structural, and functional phenotypes.
A little background: KalrnPT is a rare variant affiecting the kal-9 isoform of kalirin — a key regulator of dendrite and spine morphology via the Rac and RhoA.