Abrupt withdrawal from antiepileptic drugs is followed by increased occurrence of epileptic seizures, a phenomenon known as the “rebound effect”. By stopping treatment with levetiracetam (LEV 300 mg/kg/day, n = 15; vs saline, n = 15), we investigated the rebound effect in adult male Sprague-Dawley rats. LEV was continuously administered using osmotic minipumps, 7 weeks after the intraperitoneal administration of kainic acid (15 mg/kg). The effects of LEV were determined by comparing time intervals, treatments, and interactions between these main factors. Seizures were evaluated by video-electrocorticographic recordings and power band spectrum analysis. Furthermore, we assessed endogenous neurosteroid levels by liquid chromatography-electrospray-tandem mass spectrometry. LEV significantly reduced the percentage of rats experiencing seizures, reduced the seizure duration, and altered cerebral levels of neurosteroids. In the first week of LEV discontinuation, seizures increased abruptly up to 700% (p = 0.002, Tukey’s test). The power of delta band in the seizure postictal component was related to the seizure occurrence after LEV withdrawal (r2 = 0.73, p < 0.001). Notably, allopregnanolone hippocampal levels were positively related to the seizure occurrence (r2 = 0.51, p = 0.02) and to the power of delta band (r2 = 0.67, p = 0.004). These findings suggest a role for the seizure postictal component in the rebound effect, which involves an imbalance of hippocampal neurosteroid levels.

Memory relies on the firing of simultaneously activated neurons (engram), whose synapses are strengthened by long-term potentiation mechanisms. Optogenetic tools and a fluorescence probe to map synaptic engrams, were combined with a digital light processor device (DLP), to create in-vitro engrams and study populations of potentiated spines.

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In this proceeding we discuss the recent work involving our developed optogenetic tool, where we use digital light processor (DLP) as a light-stimulation source of neuronal culture and microelectrode array (MEA) system as the sampling unit. In this work we aim at developing an integrated experimental platform which should assist in the study of the structure and the function of neuronal networks. In particular, the setup proposed in this work should serve as an optogenetic tool for in-vitro experiments, controlled by a feedback from electrophysiological signals from the network to address specific neuronal circuits. In this manuscript some of the recent results from experiments involving optical stimulation and electrophysiological recording of neuronal cultures are shown. Additionally, we have developed an AI-based model which is trained according the recorded electrophysiological signals and reproduces the functionality and the macro-structure of the culture under test. The description and some preliminary results of this model are also discussed in this proceeding.