Venue: CARF
Thesis defended in english
Team : NeuroDTx : Neuromodulation et Thérapies Numériques
IMN
Thesis directed by Amélie Aussel, Fabien Wagner and Nicolas Rougier
Title
Computational modeling of the hippocampus with detailed neuronal morphology for the interaction of neural oscillations with extracellular electrical stimulation
Abstract
Successful encoding and retrieval of memory relies on coupling of theta (4-8 Hz) and gamma (30-100Hz) oscillations. Disruption of theta-gamma coupling is observed in pathological states such as Alzheimer’s disease. In recent years, efforts have been made to slow the progression of the disease, including the use of Deep Brain Stimulation (DBS) of the memory network. Despite extensive research, hippocampal electrical stimulation studies yield inconsistent results, limiting our understanding of its effects on neuronal dynamics and memory. To address this, I developed a reduced model of hippocampal CA1 region with multicompartment neurons to accurately simulate signal propagation and neuronal recruitment after extracellular stimulation. Three types of neurons (pyramidal, basket and OLM) were represented with respect to biological ratios taken from the literature. All neurons were modeled following the Hodgkin-Huxley formalism, and I explicitly modeled trajectories of Schaffer collaterals originating from CA3 and synapsing on pyramidal neurons of CA1. My model exhibits theta-nested gamma oscillations, balancing computational efficiency with anatomical accuracy to enable tractable and systematic investigation of stimulation parameters and their impact on network dynamics. My simulations demonstrate that bipolar biphasic stimulation induces excitation of the Schaffer collaterals, subsequently driving excitation in the CA1 network. However, when the Schaffer collaterals are removed from the model, the same stimulation protocol induces an inhibitory response within the network.
Key words
Computational neuroscience, Hippocampus, Memory, Neural oscillations, Multicompartment models, Electrical stimulation