recording-modulation-epileptiform-activity-rodent-brain-slices

Recording and Modulation of Epileptiform Activity in Rodent Brain Slices Coupled to Microelectrode Arrays

Temporal lobe epilepsy (TLE) is the most common partial complex epileptic syndrome and the least responsive to medications. Deep brain stimulation (DBS) ...

Istituto Italiano di Tecnologia

Hippocampal networks exhibit spontaneous electrophysiological activity that can be modulated by pharmacological manipulation and can be monitored over time using Micro-Electrode Arrays (MEAs), devices composed by a glass substrate and metal electrodes. The typical mode of activity of these dissociated cultures is the network-wide bursting pattern, which, if properly chemically modulated, can recall the ictal events of the epileptic phenotypes and is well-suited to study the effects of antiepileptic compounds. In this paper, we analyzed the changes induced by Carbamazepine (CBZ) and Valproate (VPA) on mature networks of hippocampal neurons in "control" condition (i.e., in the culturing medium) and upon treatment with the pro-convulsant bicuculline (BIC). We found that, in both control and BIC-treated networks, high doses (100 μM-1 mM) of CBZ almost completely suppressed the spiking and bursting activity of hippocampal neurons. On the contrary, VPA never completely abolish the electrophysiological activity in both experimental designs. Interestingly, VPA cultures pre-treated with BIC showed dual effects. In fact, in some cultures, at low VPA concentrations (100 nM-1 μM), we observed decreased firing/bursting levels, which returned to values comparable to BIC-evoked activity at high VPA concentrations (100 μM-1 mM). In other cultures, VPA reduced BIC-evoked activity in a concentration-independent manner. In conclusion, our study demonstrates that MEA-coupled hippocampal networks are responsive to chemical manipulations and, upon proper pharmacological modulation, might provide model systems to detect acute pharmacological effects of antiepileptic drugs.

Effects of antiepileptic drugs on hippocampal neurons coupled to micro-electrode arrays.

In this paper, we show that neuronal assemblies plated on Micro Electrode Arrays present synchronized, low frequency firing patterns similar to in vivo slow wave oscillations, which are a key parameter of sleep-like state. Although neuronal cultures lack the characteristic high-frequency waves of wakefulness, it is possible to modulate their spontaneous firing pattern through the administration of specific neurotransmitters such as acetylcholine. We thus stimulated the cortical cultures with an agonist of acetylcholine receptor, Carbachol, which caused a desynchronization of the spontaneous firing of the cultures. We recorded and monitored the cultures for a period of over 31 h. We analyzed the electrophysiological signals by exploiting novel methodological approaches, taking into account the different temporal scales of the recorded signals, and considering both spikes and local field potentials. Supporting the electrophysiological analysis results, gene expressions of targeted genes showed the activation of specific markers involved in sleep-wake rhythms. Our results demonstrate that the Carbachol treatment induces desynchronization of neuronal activity, altering sleep-like properties in an in vitro model. 

A Simplified In vitro Experimental Model Encompasses the Essential Features of Sleep.

[This corrects the article on p. 315 in vol. 10, PMID: 27458335.]. 

Article	Year
Effects of antiepileptic drugs on hippocampal neurons coupled to micro-electrode arrays. Frontiers in neuroengineering\| PubMed ID: 24312049	2013
A Simplified In vitro Experimental Model Encompasses the Essential Features of Sleep. Frontiers in neuroscience\| PubMed ID: 27458335	2016
Corrigendum: A Simplified In vitro Experimental Model Encompasses the Essential Features of Sleep. Frontiers in neuroscience\| PubMed ID: 27610075	2016

Ilaria Colombi

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