Psychedelics Reverse the Polarity of Long-Term Synaptic Plasticity in Cortical-Projecting Claustrum Neurons
eNeuro October 1, 2025 Tanner L. Anderson, Artin Asadipooya, Pavel I. Ortinski 3 citations
Psychedelic drugs like DOI can reverse the direction of synaptic plasticity in the claustrum, a brain region rich in serotonin 2 receptors and heavily connected to the anterior cingulate cortex. In male rats, pairing presynaptic stimuli with postsynaptic action potentials in claustrum neurons projecting to the ACC caused DOI to flip the plasticity from long-term depression to long-term potentiation, an effect specific to locally activated synapses. DOI also altered several action potential dynamics in these neurons. The findings support the idea that psychedelics induce rapid and lasting neuroplasticity and that claustrocortical circuits are especially sensitive to these drugs, offering a potential mechanism for their therapeutic effects.