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Psychedelic DOI Reverses Synaptic Polarity in Claustrum-to-ACC Circuit

Preclinical recordings in male rats show DOI drives LTP where LTD typically occurs in this 5‑HT2‑rich pathway, outlining a plausible plasticity mechanism.

Overview

  • The eNeuro paper reports that DOI switches long-term depression to long-term potentiation in claustrum neurons that project to the anterior cingulate cortex.
  • Under psychedelic exposure, activation of these neurons strengthened claustrum–ACC connectivity, an effect not seen under baseline conditions.
  • Researchers documented a dense population of serotonin 2 receptors in the claustrum and observed DOI-linked changes in action potential dynamics.
  • The team frames the findings as mechanistic support for rapid, lasting circuit plasticity that could help explain the vividness of psychedelic experiences.
  • The work uses DOI as a probe in male rats and does not establish behavioral outcomes or clinical efficacy, with translation to humans remaining an open question.