ELECTROPHYSIOLOGICAL ALTERATIONS ACROSS MEDIODORSAL THALAMUS SUBDIVISIONS IN THE SCHIZOPHRENIA <EM>GRIN2A<SUP>+/-</SUP></EM><SUP> </SUP>MOUSE

Schizophrenia is a chronic debilitating psychiatric condition affecting ~1% of the population and is characterised by heterogeneous symptomatology. The mediodorsal nucleus (MD) is a higher-order thalamic nucleus with multidimensional roles in cognitive control and sensory integration and is increasingly implicated in the pathophysiology of schizophrenia. The MD is classically divided into medial (MDm), central (MDc), and lateral (MDl) subregions characterised by distinct anatomical connectivity, molecular expression profiles, and differences in ex vivo electrophysiological metrics. However, whether these differences across MD subdivisions correspond to distinct electrophysiological signatures in vivo and how these are altered in models of schizophrenia remains unknown. Here, we perform in vivo single-neuron electrophysiological recordings with Neuropixels probes across the three MD subdivisions in awake head-fixed, adult male wildtype mice and Grin2a^+/- transgenic mice for schizophrenia under a sensorimotor behavioural task. In independent cohorts of wildtype animals, we report reliable differences in extracellular waveform properties and neural activity metrics across MD subdivisions, with MDc most distinct from MDm and MDl. Comparisons across genotypes reveal that Grin2a^+/- transgenic mice show subdivision-specific alterations across various waveform and spiking characteristics compared to wildtype controls. Together, our findings extend the parameter space of differences between MD subdivisions and illustrate that these show non-uniform alterations of in vivo electrophysiological metrics in a genetic mouse model for schizophrenia.