Rhythmic network activity in human brain slices: variability, mechanisms, and translational insights

In vitro maintained human brain slices provide a unique experimental platform for investigating rhythmic neuronal network activity, bridging the gap between animal models and clinical studies. A wide range of spontaneous and induced oscillatory activities has been described in human brain slices. However, their occurrence and characteristics are strongly shaped by methodological determinants spanning tissue origin, slice preparation, recording conditions, and induction strategies. This has been shown to have a profound impact on the reproducibility and interpretation of oscillatory dynamics. This review synthesizes current evidence on rhythmic network activity in acute human brain slices, with a particular emphasis on how methodological determinants interact with intrinsic circuit properties to generate oscillatory dynamics. We discuss how different experimental manipulations influence oscillation frequency, stability, and spatial organization. We further examine the cellular and circuit mechanisms underlying rhythmic activity, highlighting the roles of excitatory-inhibitory balance, synaptic dynamics, neuromodulatory influences, and distinct interneuron populations. Finally, we consider how oscillatory patterns differ across disease contexts, particularly epilepsy and tumor-associated cortex, and discuss the translational value and limitations of human brain slices for linking microcircuit mechanisms to pathological and functional brain states.