Biology subjects

Tass, P. A.

Publications and source records attributed to Tass, P. A..

3 recordsLinked to original sources

bioRxiv2025

Calcium-Based Synaptic and Structural Plasticity Link Pathological Activity to Synaptic Reorganization in Parkinson's Disease

Altered motor symptoms of Parkinsons disease (PD) are associated with dopaminergic neuronal loss. Widespread synaptic reorganization and neural activity changes, including exaggerated beta oscillations and bursting, follow dopamine depletion (DD) of the basal ganglia (BG). Our computational model examines DD-induced neural activity changes and synaptic reorganization. It encompasses the BG sub-circuit comprising the subthalamic nucleus and globus pallidus externus. Calcium-dependent synaptic and structural plasticity mechanisms were incorporated, allowing neural activity to alter network topology. We show how elevated iMSN firing rates can induce synaptic connectivity changes consistent with PD animal models. We suggest synaptic reorganization following DD results from a series of homeostatic calcium-based synaptic changes triggered by elevated iMSN activity. Structural plasticity counteracts DD-induced neural activity changes and opposes exaggerated beta oscillations, whereas synaptic plasticity alone amplifies beta oscillations. Our results suggest that synaptic and structural plasticity have qualitatively different contributions to DD-induced synaptic reorganization in the BG. TeaserSynaptic and structural plasticity differentially drive synaptic reorganization and abnormal activity in Parkinsons disease.

neuroscience↗

bioRxiv2024

Electrical Coordinated Reset Stimulation Induces Network Desynchronization in an in Vivo Model of Status Epilepticus

Epilepsy, a neurological disorder characterized by recurrent seizures, profoundly impacts individuals worldwide. Various electrical stimulation protocols have been investigated to mitigate epileptic seizures, among which Coordinated Reset (CR) stimulation may have potential for inducing long-lasting neural desynchronization. This study explores the acute effects of CR stimulation on synchronization dynamics during Status Epilepticus (SE) in an in vivo animal model. An electrographically sustained seizure-state was induced via 4-aminopyridine (4AP) administration to CA3. Custom-designed electrode probes were implanted to facilitate simultaneous recording and electrical stimulation. Analytical univariate and bivariate features were constructed from the LFP time-series recording. Feature metrics focused on spike synchronization metrics and continuous signal analysis of amplitude, spectral power and phase synchronization across electrode pairs and frequency bands. Significance of modulation was assessed through permutation testing of the observed differences between the CR-stimulated group (N=5) compared to the control (no stimulation) group (N=3) during SE. Results showed overall decrease in amplitude and power univariate features, and a significant modulation of bivariate synchronization and connectivity measures across the spectrum between the CR stimulation and control group. Our findings underscore the potential effectiveness of CR stimulation in attenuating excessive neural synchronization, paving the way for further exploration of CR stimulation as a viable intervention for network desynchronization of epileptiform activity and subsequently treatment of seizures.

neuroscience↗

bioRxiv2022

Decoupling of interacting neuronal populations by time-shifted stimulation through spike-timing-dependent plasticity

The synaptic organization of the brain is constantly modified by activity-dependent synaptic plasticity. In several neurological disorders, abnormal neuronal activity and pathological synaptic connectivity may significantly impair normal brain function. Reorganization of neuronal circuits by therapeutic stimulation has the potential to restore normal brain dynamics. Increasing evidence suggests that the temporal stimulation pattern crucially determines the long-lasting therapeutic effects of stimulation. Here, we tested whether a specific pattern of brain stimulations can enable the suppression of pathologically strong inter-population synaptic connectivity through spike-timing-dependent plasticity (STDP). More specifically, we tested how introducing a time shift between stimuli delivered to two interacting populations of neurons can effectively decouple them. To that end, we first used a tractable model, i.e., two bidirectionally coupled leaky integrate-and-fire (LIF) neurons, to theoretically analyze the optimal range of stimulation frequency and time shift for decoupling. We then extended our results to two reciprocally connected neuronal populations (modules) where inter-population delayed connections were modified by STDP. As predicted by the theoretical results, appropriately time-shifted stimulation causes a decoupling of the two-module system through STDP, i.e., by unlearning pathologically strong synaptic interactions between the two populations. Based on the overall topology of the connections, the decoupling of the two modules, in turn, causes a desynchronization of the populations that outlasts the cessation of stimulation. Decoupling effects of the time-shifted stimulation can be realized by time-shifted burst stimulation as well as time-shifted continuous simulation. Our results provide insight into the further optimization of a variety of multichannel stimulation protocols aiming at a therapeutic reshaping of diseased brain networks.

neuroscience↗