WHOLE BRAIN MAP OF DEVELOPING PARVALBUMIN INTERNEURON NETWORKS IN MOUSE MODELS OF SCHIZOPHRENIA

Schizophrenia (SZ) is a neurodevelopmental disorder affecting over 23 million people worldwide and accounting for ~50% of all mental health hospitalizations. It is characterised by positive, negative and cognitive symptoms, including distortions of thoughts, perception and emotions whose onset typically occurs during adolescence. There are numerous genetic risk factors for SZ, including copy number variant mutations, such as the 22q11.2 deletion syndrome (DS), in addition to rare coding variants, such as GRIN2A mutations associated with N-methyl-D-aspartate receptor hypofunction. A common feature of the postmortem SZ brain is a marked reduction in parvalbumin (PV) expression in a subset of GABAergic interneurons. PV interneurons are key regulators of brain development, and their maturation, which can be assessed through the formation of extracellular structures termed perineuronal nets (PNNs), is thought to be disrupted in SZ. This study aims to compare the adolescent maturation of PV cells in different mouse models of SZ to uncover common developmental alterations across diverse cortical and subcortical structures. To investigate this, we compared 22q11.2 DS, GRIN2A mutant mice and their littermate controls pre- and post-adolescence. We performed immunohistochemical staining for PV and PNNs by labelling Wisteria floribunda Agglutinin (WFA). We imaged sequential brain slices, registered images to the Allen Brain Atlas using an AI-based image registration pipeline and quantified PV and WFA cell density, intensity and colocalization across the whole-brain. These findings provide insight into when and how these mutations affect inhibitory networks establishment, which could contribute to altered brain function in SZ.