Section: New Results

From the Microscopic to the Mesoscopic Scale

Participants: Laure Buhry, Axel Hutt, Francesco Giovannini, Jean-Baptiste Schneider

In collaboration with LieJune Shiau (University of Houston)

To improve our understanding of the effects of anaesthesia on the neural correlates of memory, we focussed on how anaesthetics disrupt the interaction between the hippocampus and the cerebral cortex. As a first step towards this objective Francesco Giovannini modelled a hippocampal pyramidal neuron using the Hodgkin-Huxley model capable of exhibiting long-lasting persistent firing activity when subject to a strong transient stimulus [16] . This behaviour is underlay by an intrinsic membrane current activated by the increase of intracellular calcium ions, following the discharge of an action potential by the neuron, in accord with that displayed in neural recordings of hippocampal slice preparations. Connecting these persistent firing neurons in a network comprising strong local excitation yields a wide range of behaviours depending on the interaction between CAN and synaptic currents. Indeed, the network model is capable of displaying rhythmic behaviour in the form of short synchronised bursts with intra-burst frequencies of $20-40Hz$ and inter-burst frequencies of $3Hz$. Furthermore, coupling CAN-equipped pyramidal neurons with a population of fast-spiking inhibitory interneurons yields emerging synchronous activity whose frequency is modulated by the strength of this coupling. These results hint towards a possible mechanism for the generation of memory-related oscillatory activity in the hippocampus.

We investigated the effects of propofol-mediated tonic inhibition on the synchronous activity elicited in a network of hippocampal inhibitory interneurons. This work was conducted in collaboration with Jean-Baptiste Schneider, as part of hist 2-month internship. We studied the effect of propofol-induced tonic inhibition on the oscillations elicited in a network of hippocampal Hodgkin-Huxley gamma-aminobutyric acid ($GABA$) interneurons by studying the action of propofol on extrasynaptic GABAergic receptors. Our results [15] show that increasing doses of propofol reduce the overall network activity and slow down its oscillations until a critical value at which the synchronisation increases abruptly at values of twice the synchronisation displayed in the absence of tonic inhibition, and the mean firing rate increases. This emergence of synchronous activity mediated by anaesthetic perfusion point towards a possible mechanism for the emergence of paradoxical excitation under general anaesthesia.

In this context, Laure Buhry works with LieJune Shiau (University of Houston) on a better understanding of the models used by the community of computational neuroscientists. The goal is to show in which extent models are comparable or interchangeable. We focus on the comparison of oscillatory mechanisms of neuronal populations in different spiking models, especially in the Hodgkin-Huxley and the adaptive exponential integrate-and-fire model (AdEx). Especially, we have shown that a same number of synaptic connection per neuron is necessary to elicit synchronization in inhibitory neural networks of adaptive exponential integrate and fire neurons as in networks of Hodgkin-Huxley neurons. We have also conducted an extensive study regarding the effects of the different parameters of the AdEx model on the synchronization mechanisms in inhibitory neural networks, particularly in the context of gamma oscillations. A manuscript will be submitted soon to the Journal of Computational Neuroscience.

We have continued working on the effect of additive noise on neural oscillations and have shown that additive noise modulates the frequency of self-sustained neural rhythms [3] .