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.

Summary Recent advances in bioelectronics and neural engineering allowed the development of brain machine interfaces and neuroprostheses, capable of facilitating or recovering functionality in people with neurological disability. To realize energy-efficient and real-time capable devices, neuromorphic computing systems are envisaged as the core of next-generation systems for brain repair. We demonstrate here a real-time hardware neuromorphic prosthesis to restore bidirectional interactions between two neuronal populations, even when one is damaged or missing. We used in vitro modular cell cultures to mimic the mutual interaction between neuronal assemblies and created a focal lesion to functionally disconnect the two populations. Then, we employed our neuromorphic prosthesis for bidirectional bridging to artificially reconnect two disconnected neuronal modules and for hybrid bidirectional bridging to replace the activity of one module with a real-time hardware neuromorphic Spiking Neural Network. Our neuroprosthetic system opens avenues for the exploitation of neuromorphic-based devices in bioelectrical therapeutics for health care.

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.