Biophysical Modeling of Thalamocortical Circuit Dynamics: Species-Specific Insights into Neural Synchrony, Sleep Spindles, and Mechanisms of Neuropsychiatric Disorders

Abstract Thalamocortical circuits play a fundamental role in cognitive functions, and neural synchronization, with disruptions implicated in disorders. Here, we investigated the neural dynamics of thalamocortical connectivity using computational modeling of rodent and primate thalamocortical loops. We incorporated distinct projections and varying network configurations and examined their impact on circuit synchrony, spiking patterns, and sleep spindle generation. Circuits included distinct core and matrix thalamocortical projections, with core pathways providing focal, driving input to middle cortical layers, while matrix pathways mediate widespread, modulatory signaling across superficial layers, and the presence of thalamic interneurons, which are scarce in rodents but comprise up to a third of the thalamic neurons in primates. In our simulations, these distinctions produced clear species-and loop architecture-dependent effects: rodent circuits were markedly more sensitive to parameter changes in core and matrix thalamocortical connectivity strength, while primate circuits maintained relatively stable spatiotemporal patterns across parameter variations, exhibiting greater stability and synchrony. Sleep spindle analysis likewise revealed species differences. Overall, across all thalamocortical configurations, rodent simulations produced spindles with greater spatiotemporal variability, showing irregular event structure and timing. In contrast, primate spindles were more uniform and coherent, with clearer and more consistent organization across neurons and time. These findings provide insights into species-specific differences in thalamocortical dynamics and have implications for modeling sensory and cognitive disruptions in disorders such as autism and schizophrenia. By incorporating distinct configurations, and interspecies differences, our model contributes to understanding how thalamocortical dysregulation may differentially impact spindle generation, network synchrony, and information processing across species.