Can neuronal cell cultures become more physiologically relevant if we train them during their development? How Organics.AI aims to move CNS drug screening towards closed-loop functional phenotypic screening.
What Can Organics.AI Contribute to CNS Drug Screening?
Can we make neuronal cell cultures more physiologically relevant by training them during their development?
With Organics.AI, we aim to introduce new approaches to neuronal stimulation and electrophysiological recording that could significantly expand the capabilities of in vitro CNS drug screening.
From passive cultures to conditioned neuronal networks
Traditionally, neuronal cultures develop largely without structured external stimulation. Organics.AI aims to change this by introducing controlled electrical stimulation early in culture development and continuing throughout neuronal maturation.
Through repeated stimulation and feedback, neuronal networks may develop activity patterns and adaptive responses that more closely resemble aspects of neuronal processing in vivo.
Towards functional screening of cognitive processes
A major challenge in CNS drug development is the limited ability of current in vitro models to reproduce and quantify cognitive functions.
Using new stimulation and recording paradigms with rapid closed-loop feedback, we aim to investigate learning, adaptation, and memory-like processes in living neuronal networks.
This could open new opportunities for evaluating compounds that enhance or impair neuronal information processing, particularly in drug development for neurodegenerative diseases.
Gamma oscillations as functional biomarkers
Another important research direction is the investigation of gamma-band oscillations in conditioned neuronal networks.
Gamma oscillations, typically in the 30–100 Hz frequency range, are associated with several brain functions, including attention, sensory processing, and memory.
Gamma-band activity is also relevant to anesthesia research, where changes in oscillatory activity can provide information about brain states and anesthetic effects.
If reproducible gamma oscillations can be established and characterized in conditioned neuronal cultures, they could provide additional functional readouts for CNS drug screening, including the evaluation of anesthetic compounds.
In our unpublished experiments, we observed gamma-band oscillations in electrically conditioned neuronal cultures using a stimulation protocol based on Leondopulos et al. (2012). These preliminary findings provide a starting point for further investigation of gamma-band activity as a functional screening parameter.
Our objective with Organics.AI is to move beyond measuring neuronal activity alone — towards measuring how living neuronal networks process information, adapt, and respond to pharmacological interventions.
With Organics.AI, we aim to advance CNS drug discovery from passive electrophysiological screening towards closed-loop functional phenotypic screening.
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