Inferring stimulation induced short-term synaptic plasticity dynamics using novel dual optimization algorithm

PLoS One. 2022 Sep 21;17(9):e0273699. doi: 10.1371/journal.pone.0273699. eCollection 2022.

Abstract

Experimental evidence in both human and animal studies demonstrated that deep brain stimulation (DBS) can induce short-term synaptic plasticity (STP) in the stimulated nucleus. Given that DBS-induced STP may be connected to the therapeutic effects of DBS, we sought to develop a computational predictive model that infers the dynamics of STP in response to DBS at different frequencies. Existing methods for estimating STP-either model-based or model-free approaches-require access to pre-synaptic spiking activity. However, in the context of DBS, extracellular stimulation (e.g. DBS) can be used to elicit presynaptic activations directly. We present a model-based approach that integrates multiple individual frequencies of DBS-like electrical stimulation as pre-synaptic spikes and infers parameters of the Tsodyks-Markram (TM) model from post-synaptic currents of the stimulated nucleus. By distinguishing between the steady-state and transient responses of the TM model, we develop a novel dual optimization algorithm that infers the model parameters in two steps. First, the TM model parameters are calculated by integrating multiple frequencies of stimulation to estimate the steady state response of post-synaptic current through a closed-form analytical solution. The results of this step are utilized as the initial values for the second step in which a non-derivative optimization algorithm is used to track the transient response of the post-synaptic potential across different individual frequencies of stimulation. Moreover, in order to confirm the applicability of the method, we applied our algorithm-as a proof of concept-to empirical data recorded from acute rodent brain slices of the subthalamic nucleus (STN) during DBS-like stimulation to infer dynamics of STP for inhibitory synaptic inputs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Deep Brain Stimulation* / methods
  • Electric Stimulation
  • Humans
  • Neuronal Plasticity / physiology
  • Subthalamic Nucleus* / physiology
  • Synaptic Potentials

Grants and funding

This study was supported by the following grants and scholarships: Natural Sciences and Engineering Research Council of Canada, RGPIN-2020-05868 (M.L) AGEWELL, UofT FASE Graduate Student and Postdoctoral Award in Technology and Aging (A.G.); Deutsche Forschungsgemeinschaft (DFG, German Research Fundation) Project ID 424778381 TRR 295 (L.A.S.); Junior Clinician Scientist Program of the Berlin Institute of Health (L.A.S.); German Academic Exchange Service, DAAD (L.A.S.); Brain Canada Foundation (L.M.); Walter and Maria Schroeder Foundation (L.M.) M.L. designed the study, A.G. and M.L. analyzed data and developed dual optimization algorithm. L.A.S collected data (related to a previously published study). A.G. and M.L. wrote the manuscript, L.A.S and L.M. contributed in the preparation of the manuscript. A.G., L.A.S, M.R.P, L.M, and M.L. revised and edited the manuscript.