P106 Computational and Experimental Insights into Hippocampal Slice Spiking under Extracellular Stimulation
Sarah Hamdi Cherif*1,2,3, Mathilde Wullen4, Steven Le Cam2, Valentine Bouet4, Jean-Marie Billard4, Jérémie Gaidamour3, Laure Buhry1 , Radu Ranta2
1Université de Lorraine, CNRS, LORIA, France
2Université de Lorraine, CNRS, CRAN, France
3Université de Lorraine, CNRS, IECL, France
4 Normandie Univ, UNICAEN, CHU Caen, INSERM, CYCERON, COMETE, France
*Email: sarah.hamdi-cherif@loria.fr
Introduction
Synaptic plasticity and neuronal excitability in the hippocampus (HC) are altered in schizophrenia [1]. Multi Electrode Array (MEA) recordings following a long-term potentiation (LTP) protocol revealed local field potential (LFP) variations along physiological pathways and high-frequency (HF) activity near the stimulation site [2]. To understand the effect of extracellular stimulation (ES) and explore its relationship with synaptic activity and spike generation, we combined electrophysiological recordings and computational modelling. We applied ES to hippocampal slices around Schaeffer’s collaterals while recording signals near CA3 pyramidal cell bodies, and we developed a computational model to aid interpretation.
Methods
Experiments: in-depth glass microelectrode recordings in CA3 of healthy HC slices. 40 pulses (0.4 ms duration, 7 s apart) at 0.2, 0.4 mA. Signals were processed and filtered above 300 Hz to isolate spiking activity.
Simulations: one multi-compartment CA3 pyramidal neuron model [3], with ES modelled using LFPy as a dipole [4], orthogonal to Schaffer collaterals. Background noise below spiking level was added to reflect environmental HC conditions. We varied the position of the stimulation along the axon and at different distances to explore spike variability. Synaptic inputs included excitatory (dendritic) and inhibitory (somatic) drive [5], generated by a variable-rate Poisson process, simulating activation of cells located closer to the ES.
Results
In the experimental data, each ES pulse triggered a single spike, issued from the same cell according to tentative spike sorting [6]. Lower pulse intensity led to variable latencies. As intensity increased, spike timing arose earlier and became more synchronized(Fig.1.a).
According to our simulations (Fig.1.b), a cell, activated directly by ES, showed spike latencies of 0.25–4 ms that were used to parametrize the Poisson process. The target cell, excited both by ES and synaptic inputs, exhibited later and more dispersed latencies, of 3-8 ms, closer to experimental data, suggesting they capture further-layer activity. Higher intensity had the same effects as experimental data (Fig.1.c).
Discussion
Our findings suggest that the HF activity observed in the MEA recordings results from spiking activity propagating antidromically within CA3, activating recurrent excitatory networks. We plan more recordings to confirm our findings and use the model to include the reproduction of LFP dynamics, focusing on synaptic activity. Also, to work on simulating populations while reducing the cell-models to point-neurons and implementing a network parametrized using the observed spike latencies to approximate its dynamics. Ultimately, we aim to develop a comprehensive computational model of HC electrical activity and synaptic plasticity, in healthy and schizophrenia mouse models [7], to better understand the mechanisms involved.
Figure 1. Figure 1 - (a) Experimental trials at 200µA (left) and 400µA (right), (b) Simulated membrane potentials at 100µA (left) and 250µA (right). Both trials and simulations last 50 ms, with stimulation starting at 5 ms. (c) Boxplots comparing spike latency variability across low/high intensities in both experiment (left) and simulation (right).
Acknowledgements
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References
[1]https://doi.org/10.3390/ijms22052644
[2]https://doi.org/10.12751/nncn.bc2024.244
[3]https://doi.org/10.1523/JNEUROSCI.1889-24.2025
[4]https://doi.org/10.1007/978-1-61779-170-3_8
[5]https://doi.org/0.3389/fncel.2013.00262.
[6]https://doi.org/10.1088/1741-2552/acc210
[7]https://doi.org/10.1016/j.schres.2020.11.043
