A MULTICOMPARTMENT CA1 HIPPOCAMPAL MODEL WITH EXPLICIT SCHAFFER COLLATERAL INPUTS TO INVESTIGATE THE EFFECTS OF ELECTRICAL STIMULATION ON THETA-GAMMA OSCILLATIONS

Memory encoding and retrieval rely on hippocampal theta–gamma coupling, which is disrupted in memory disorders. Despite extensive research, hippocampal electrical stimulation studies yield inconsistent results, limiting our understanding of its effects on neuronal dynamics and memory. To address this, we developed a reduced model of the CA1 area with multicompartment neurons to accurately simulate signal propagation and neuronal recruitment after extracellular stimulation.
The model was implemented as a slice of the CA1 area. Three types of neurons (pyramidal, basket and OLM) were represented with respect to biological ratios taken from the literature. They followed the Hodgkin-Huxley formalism. Explicit trajectories of Schaffer collaterals originating from CA3 and synapsing on pyramidal neurons of CA1 were also modeled. Connections between neurons were distance-based following biological data and connection weights were optimized to enhance gamma activity.
The Schaffer collaterals were driven by 6Hz oscillatory inputs to emulate endogenous theta rhythms in CA3 projecting to CA1. We observed that gamma-band activity, synchronized with the ongoing theta rhythm, emerged in all neuronal populations. Preliminary results of extracellular stimulation indicate that high-amplitude stimulations tended to reduce Schaffer collateral activity, while enhancing the activity of basket cells. This led to the inhibition of surrounding pyramidal neurons. In contrast, low-amplitude stimulations recruited the Schaffer collaterals, resulting in enhanced activity of connected pyramidal neurons.
To conclude, we built a reduced model of the hippocampal CA1 balancing computational efficiency with anatomical accuracy. This model enables tractable and systematic investigation of stimulation parameters and their impact on network dynamics.