CLOSED-LOOP CONNECTIVITY BEST SUPPORTS INFORMATION PROCESSING AND SLEEP DYNAMICS IN THE MOUSE THALAMO-CORTICAL WHISKER PATHWAY: A COMPUTATIONAL STUDY

Despite recent advancements in mapping thalamic and cortical projections, the specific organization of intrathalamic connectivity remains elusive. Current experimental approaches cannot definitively determine whether these connections are arranged in reciprocal (closed-) or non-reciprocal (open-loop) circuits. Understanding the organization of intrathalamic projections could fundamentally reshape our view of thalamic processing. Closed-loop circuits may promote localized and recurrent processing, whereas open-loop circuits may facilitate broader integration of signals across thalamic regions. Computational modeling provides an alternative for probing the functional consequences of different intrathalamic architectures, circumventing experimental limitations. With this in mind, we developed a biophysically detailed multi-compartmental model of the mouse whisker pathway, built on anatomical and physiological data. Our goal was to determine whether closed- or open-loop connectivity can best reproduce key characteristics of cell and network responses in the mouse whisker pathway across wakefulness and sleep. We showed that closed-loop connectivity between the thalamocortical (TC) relay neurons in the ventral posteromedial nucleus and the inhibitory interneurons in the thalamic reticular nucleus (TRN) best reproduces thalamic spiking and local field potential responses across awake and sleep states. In this model, feedforward (TC→TRN) on-center projections (i.e., spatially aligned) regulate the angular tuning in the awake state, while on-center feedback (TRN→TC) supports spindle oscillations during sleep. We also showed that direct activation of closed-loop corticothalamic feedback (CT→TC and CT→TRN) by TC inputs can sharpen the angular tuning in the thalamus. These results underscore the importance of closed-loop connectivity in unifying wake and sleep dynamics, offering insights into how thalamo-cortical circuits balance precise sensory tuning with robust oscillatory rhythms across behavioral states.

Citation

Moreira, J. (2025). CLOSED-LOOP CONNECTIVITY BEST SUPPORTS INFORMATION PROCESSING AND SLEEP DYNAMICS IN THE MOUSE THALAMO-CORTICAL WHISKER PATHWAY: A COMPUTATIONAL STUDY [Doctoral dissertation, SUNY Downstate Health Sciences University]. SUNY Open Access Repository. https://soar.suny.edu/handle/20.500.12648/17001

CLOSED-LOOP CONNECTIVITY BEST SUPPORTS INFORMATION PROCESSING AND SLEEP DYNAMICS IN THE MOUSE THALAMO-CORTICAL WHISKER PATHWAY: A COMPUTATIONAL STUDY

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