Psychedelics Reverse the Polarity of Long-Term Synaptic Plasticity in Cortical-Projecting Claustrum Neurons

Area of Science:

• Neuroscience
• Psychopharmacology
• Synaptic Plasticity

Background:

• Psychedelic drugs show therapeutic potential for psychiatric disorders.
• The claustrum (CLA) has dense serotonin 2 receptors (5-HT2Rs) activated by psychedelics.
• Claustrocortical circuits are implicated in psychiatric disease states.

Purpose of the Study:

• Investigate the effects of psychedelics on synaptic plasticity in CLA-ACC neurons.
• Explore DOI's impact on long-term depression (LTD) and long-term potentiation (LTP).
• Characterize DOI's effects on intrinsic electrophysiological properties of CLA-ACC neurons.

Main Methods:

• Used paired-pulse stimulation and postsynaptic action potentials (APs) on CLA-ACC neurons in male rats.
• Applied the psychedelic drug 2,5-dimethoxy-4-iodoamphetamine (DOI).
• Recorded intrinsic electrophysiological properties and synaptic plasticity.

Main Results:

• DOI reversed synaptic plasticity from LTD to LTP in CLA-ACC synapses.
• DOI application altered AP dynamics in CLA-ACC neurons.
• Synaptic plasticity changes were specific to locally stimulated synapses.

Conclusions:

• Psychedelics like DOI induce rapid and lasting synaptic plasticity.
• Claustrocortical circuits are highly sensitive to psychedelic drug action.
• Findings support the hypothesis that psychedelics promote neuroplasticity for therapeutic benefits.