Background: Synaptic plasticity is an essential process encoding fine-tuned brain functions, but models to study this process in adult human systems are lacking. Objective/Hypothesis: We aim to test whether ex vivo organotypic culture of post-mortem adult brain explants (OPAB) retain synaptic plasticity. Methods: OPAB were seeded on 3D microelectrode arrays to measure local field potential (LFP). Paired stimulation of distant electrodes was performed over three days to investigate our capacity to modulate specific neuronal connections. Results: Long-term potentiation (LTP) or depression (LTD) did not occur within a single day. In contrast, after two and three days of training, OPABs showed a significant modulation of the paired electrodes’ response compared to the non-paired electrodes from the same array. This response was alleviated upon treatment with dopamine. Conclusion(s): Our work highlights that adult human brain explants retain synaptic plasticity, offering novel approaches to neural circuitry in animal-free models.