Modeling Astrocyte-Driven Repair of Visuomotor Deficits in Alzheimer's Thalamic Circuitry

Dasgupta, Madhuleena and Konar, Amit and Nagar, Atulya K (2026) Modeling Astrocyte-Driven Repair of Visuomotor Deficits in Alzheimer's Thalamic Circuitry. IEEE Transactions on Computational Biology and Bioinformatics. pp. 1-12. ISSN 1545-5963

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Abstract

Alzheimer's Disease (AD) frequently manifests in visuomotor impairments, disrupting cholinergic signaling from the brainstem to the Thalamic Reticular Nucleus (TRN). The contribution of this work lies in the development of a biologically informed computational framework to model astrocyte mediated restoration of synaptic transmission, measured by a 'release probability (PR)' in TRN under cholinergic depletion. The model simulates three physiological states-healthy, damaged, and recovered by incorporating dual astrocytic mechanisms i.e., depolarization induced suppression excitation (DSE) and endocannabinoid mediated synaptic potentiation (e-SP). This is validated through in-vivo experiments conducted using functional near-infrared spectroscopy (fNIRS) in mice, performing visuomotor integration tasks. Both computational simulations and experimental measurements demonstrate that astrocytic feedback from functional thalamocortical relay cells (TCR) and interneurons (IN) can restore PR partially to approximately 70% of healthy levels despite complete ACh depletion. The bounded, asymmetric temporal dynamics, consistent with beta distribution characteristics reflect biologically realistic regulatory mechanisms maintaining synaptic homeostasis, exhibiting rapid initial potentiation followed by gradual decay. Sensitivity analyses reveal that when modulated with identical parameter values, excitatory TCR terminals produce greater PR with increasing astrocytic strengthening rate of indirect signaling, while inhibitory IN terminals dominate PR recovery under elevated astrocyte synapse coupling weights of indirect signaling. This highlights how excitatory and inhibitory astrocyte-targeted pathways work in tandem to shape recovery in a coordinated manner. The quantitative agreement between computational predictions and experimental measurements (within 2% error) provides evidence supporting astrocyte-based neuromodulation as a biologically grounded mechanism for restoring visuomotor function in AD.

Item Type:	Article
Faculty / Department:	Faculty of Human and Digital Sciences > School of Computer Science and the Environment
SWORD Depositor:	RISE Symplectic
Depositing User:	RISE Symplectic
Date Deposited:	22 May 2026 09:00
Last Modified:	22 May 2026 09:00
URI:	https://hira.hope.ac.uk/id/eprint/4900

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