KETAMINE: Neural- and network-level changes

Abstract

Ketamine is a widely used clinical drug that has several functional and clinical applications, including its use as an anaesthetic, analgesic, anti-depressive, anti-suicidal agent, among others. Among its diverse behavioral effects, it influences short-term memory and induces psychedelic effects. At the neural level across different brain areas, it modulates neural firing rates, neural tuning, brain oscillations, and modularity, while promoting hypersynchrony and random connectivity between neurons. In our recent studies we demonstrated that topical application of ketamine on the visual cortex alters neural tuning and promotes vigorous connectivity between neurons by decreasing their firing variability. Here, we begin with a brief review of the literature, followed by results from our lab, where we synthesize a dendritic model of neural tuning and network changes following ketamine application. This model has potential implications for focused modulation of cortical networks in clinical settings. Finally, we identify current gaps in research and suggest directions for future studies, particularly emphasizing the need for more animal experiments to establish a platform for effective translation and synergistic therapies combining ketamine with other protocols such as training and adaptation. In summary, investigating ketamine’s broader systemic effects, not only provides deeper insight into cognitive functions and consciousness but also paves the way to advance therapies for neuropsychiatric disorders.