In collaboration, Drs. Konstantina Bampali from the University of Copenhagen and Sophion’s Kim Boddum have made great strides in using the Qube 384 automated patch clamp (APC) platform for recording α5-containing GABAA receptors in acutely isolated, primary neurons.

Their studies underscore the critical importance of using native, primary hippocampal neurons to assess the effects of antipsychotic compounds on GABAergic activity, particularly in the context of drug discovery for cognitive function and schizophrenia. While previous studies have relied on heterologous expression systems, such as HEK cells expressing α5-containing GABAA receptors, this research highlights the value of examining these effects in primary hippocampal neurons, more accurately reflecting the physiological environment.

α5-containing GABAA receptors, predominantly found in the hippocampus, play a key role in cognitive processes and have been implicated in the pathophysiology of schizophrenia. The use of primary neurons allows for a more nuanced and complex understanding of how antipsychotic compounds interact with these receptors in their native environment, offering insights that are crucial for developing more effective treatments for cognitive impairment, psychosis, and schizophrenia.

The study utilized Qube 384 APC technology to achieve a 65% success rate in recording from dissociated mouse hippocampal neurons. The findings revealed that many antipsychotic compounds significantly inhibit GABA-induced currents in these native neurons, reflecting their potential to modulate GABAergic activity in a more physiologically relevant context. This inhibition was consistent with results obtained in α5β3γ2 GABAA receptors expressed in HEK cells.

By focusing on native hippocampal neurons, this research provides a more physiologically relevant and reliable foundation for drug discovery, particularly in identifying compounds that can modulate cognitive function through their effects on GABAergic signaling. This approach could lead to the development of more targeted and effective antipsychotic therapies, with improved outcomes for patients with schizophrenia and cognitive impairments.