Work

A Key Regulator of Dendritic Morphology in Supragranular Neocortex Impacts Mismatch Negativity

Year: 2026

Type: preprint

Abstract: Background Cytoskeletal structure and neuronal function are heavily intertwined, and altered pyramidal neuron morphology (e.g., reduced dendritic arbors) has been consistently identified in the neocortex of individuals with psychiatric disorders. A missense mutation in Kalrn ( Kalrn -PT) enhances activation of RhoA, a cytoskeletal regulator, and leads to adolescent-onset dendritic regression in supragranular auditory cortex. To investigate the relationship between this spatiotemporally altered cytoskeletal structure and psychiatric-relevant dysfunction, we examine the functional impacts of this genetic mutation, focusing on mismatch negativity – a common biomarker of altered sensory integration that matures across adolescence. Methods In Kalrn -PT and littermate wild-type mice, pyramidal dendritic morphology was assessed across primary visual cortex (V1) layers using Golgi staining (n=172 neurons/26 mice). Local field potentials (LFPs) and neuronal spiking were recorded during a visual oddball sequence (n=25 mice). Deviance detection – the rodent neural analogue of mismatch negativity – was analyzed across V1 layers. Results Kalrn -PT mice exhibit reductions in V1 dendritic length specific to layer 2/3, mirroring observations in post-mortem samples from people with psychiatric disorders. Deviance detection was reduced in LFPs from Kalrn -PT mice and absent in layer 2/3 neurons, despite typical feature selectivity and firing rates. These deficits were accompanied by reduced functional connectivity between visual and frontal areas. Conclusions These results highlight alterations in higher-level sensory cortical integration in Kalrn -PT mice and demonstrate that adolescent-onset, disease-relevant structural and functional phenotypes can be linked by a common upstream effector. Further, these alterations appear restricted to supragranular layers, demonstrating an outsized role for Kalrn , particularly longer isoforms, in superficial neocortex.

Source: bioRxiv (Cold Spring Harbor Laboratory)

DOI: 10.64898/2026.01.28.702244