Closed-Loop Connectivity Best Supports Angular Tuning and Sleep Dynamics in a Biophysical Thalamocortical Circuit Model

Despite recent advancements in mapping thalamic and cortical projections, the specific organization of intrathalamic and corticothalamic connectivity remains elusive. Current experimental approaches cannot definitively determine whether these connections are arranged in reciprocal (closed-) or non-reciprocal (open-loop) circuits. We developed a biophysically detailed multi-compartmental model of the mouse whisker pathway, built on anatomical and physiological data. We showed that closed-loop intrathalamic projections between the thalamocortical (TC) relay neurons in the ventral posteromedial nucleus and the inhibitory neurons in the thalamic reticular nucleus (TRN) best reproduce thalamic spiking and local field potential responses across awake and sleep states. Increasing the percentage of closed-loop projections regulates the angular tuning in the awake state, while also supporting spindle oscillations during sleep. We also showed that direct activation of closed-loop corticothalamic feedback (CT[->]TC and CT[->]TRN), simulating TC inputs, sharpens the angular tuning in the thalamus. These results contribute to resolving a long-standing question regarding the organization of intrathalamic projections, offering insights into how thalamo-cortical circuits balance precise sensory tuning with robust oscillatory rhythms across behavioral states. Moreover, all model resources are open-source and available to other researchers interested in studying thalamocortical circuits. Author summaryA long standing question in the study of thalamocortical interactions is whether neurons in the thalamus form so-called open- or closed-loops when they project within the thalamus and to the cortex. In this study, we used a detailed computational model of the thalamic neurons in the whisker pathway of the mouse with realistic biophysics to investigate this question. We evaluated the impact of different connectivity arrangements in reproducing the activity of thalamic neurons observed during wakefulness and sleep. Our results show that a closed-loop circuit arrangement provides the best alternative to reproduce wake and sleep neuronal responses, highlighting the importance of computational modeling as a tool to disentangle thalamic circuit organization. We also showed that closed-loop projections from the cortex to the thalamus help further amplify the selectivity of thalamic neurons, suggesting a similar organization of corticothalamic projections. We hope our predictions can inform future experiments, and elucidate principles of thalamocortical connectivity that can be generalized across other thalamocortical motifs besides the whisker pathway and across species.