The psychedelic DOI shifted claustrum-to-anterior-cingulate synapses in male rats from depression toward potentiation.
Evidence
This preclinical electrophysiology study paired presynaptic stimulation with postsynaptic action potentials in ACC-projecting claustrum neurons from male rats, with and without DOI exposure.
Caveat
The findings are limited to an acute rat brain-circuit preparation and do not show behavioral or therapeutic effects in psychiatric disease.
Simplified
Psychedelic drugs have garnered increasing attention for their therapeutic potential in treating a variety of psychiatric diseases, such as depression, anxiety, and substance use disorder. The claustrum (CLA), a brain area with remarkable interconnectivity to frontal cortices, has recently been shown to have a dense population of serotonin 2 receptors (5-HT2Rs) that are activated by psychedelics. Because psychedelic therapy can require as little as one treatment session, it has been speculated that psychedelics achieve their long-term remedial effects by inducing neuroplasticity in brain areas responsible for psychiatric disease states, such as the anterior cingulate cortex (ACC). However, the effects of psychedelics on in serotonin receptor-rich brain areas remain entirely unexplored. We applied presynaptic stimuli paired with postsynaptic action potentials (APs) to a subpopulation of CLA neurons projecting to ACC in male rats to find that the psychedelic drug, 2,5-dimethoxy-4-iodoamphetamine (DOI), reverses the polarity of synaptic plasticity from (LTD) to (LTP) in a manner that may reflect contribution of excitatory or inhibitory neurotransmission but is specific to synapses activated by local electrical stimulation. Additionally, we characterize intrinsic electrophysiological properties of CLA-ACC neurons with and without DOI application, noting several changes to AP dynamics induced by DOI. These findings align with the view that psychedelics induce rapid and lasting synaptic plasticity and strengthen the hypothesis that claustrocortical circuits are highly sensitive to psychedelic drug action.
Key numbers
5.580
Increase in synaptic efficacy
Cohen's d value for induction with application.
8.627
observed in control conditions
Cohen's d value for in without .
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