Psychedelics activate neurons...right?

Read the F***ing Literature Dude!

I visited several neuroscientists in Germany last week and many of them had the same question:

You tell us psychedelics activate Layer Va neurons but when we look at the whole brain we see inhibition?

“Dr. Roth: you are wrong!”

I then ask them—please read this paper of mine I published 16 years ago (>1110 citations).

Parenthetically I have recently learned that the quickest way to turn someone off is to say: “Don’t you ever read the literature?”

So….basically what we show is that when we acutely activate only Pyramidal Neurons via hM3Dq the end result is activation of interneuron firing and enhancement of gamma-band activity. I note the cortical expression is very similar to the distribution of 5-HT2A receptors:

I note an essentially identical result when Layer VI neurons were driven by ChR2 was recently reported (though they ignored our prior finding).

This is (sort of) predicted by the PING model (from this paper) which posits that Gamma is driven by pyramidal neuron activation of interneurons.

My guess is that this is simply the brain’s way of maintaining E:I balance.