But when it comes to behavior, the two cell types diverge.
Normally, psilocybin can reverse stress-related behaviors. When we inactivate PT neurons before administering psilocybin, the drug’s ameliorating effects disappeared. Silencing the IT neurons had no effect.
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Normally, psilocybin can reverse stress-related behaviors. When we inactivate PT neurons before administering psilocybin, the drug’s ameliorating effects disappeared. Silencing the IT neurons had no effect.
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Comments
The results highlight PT neurons as key to the long-term antidepressant-like effects of psilocybin.
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Psilocybin increases calcium activity in the apical dendrites of PT neurons, but not IT neurons.
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It has long been debated whether serotonin 2A receptor is needed. We took a precise approach, using a conditional knockout mouse to show that deleting the receptor in frontal cortex abolishes psilocybin’s long-term behavioral effects.
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These are strong evidence supporting the role of serotonin 2A receptors in psychedelic drug action.
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The short- and long-term effects of psilocybin are mediated by different circuits, with the PT neurons in frontal cortex sitting at the core of the long-term response.
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