Fig. 5: Cortical network model predicts 5-HT2A receptor-induced modulations in activity.
a Left: Schematics of the spiking network model showing interactions between different pools of neurons (excitatory, inhibitory), activation of the 5-HT2A receptor, and visual input. 5-HT2A receptor activation in only excitatory units revealed changes in spontaneous firing (middle) and stimulus-evoked magnitude (right) for excitatory units (dark orange) and inhibitory units (light blue) dependent on the percentage of excitatory units with activated 5-HT2A receptors. b 5-HT2A receptor activation in only inhibitory units. Same analysis as in (a). Color saturation in (a, b) indicates that the 5-HT2A receptor was activated in the analyzed type of unit (“direct effect”, dark colors) or instead affects the analyzed unit via (poly-) synaptic contacts (“indirect network effects”, light colors,); color scheme as in Figs. 2 and 3. c Mean-driven regime: Predicted effects of “systemic” activation (simultaneous activation of 5-HT2A in both excitatory and inhibitory units) on baseline firing (middle) and visual response magnitude (right) assuming linear superposition of the model values shown in (a, b). Blue shaded area marks the range of suppression of visual gain observed for systemic activation in the current study (−32% and −25% (average across stim #2–4) for excitatory (orange stippled line) and inhibitory neurons (light blue stippled line), respectively) and of presumably 5-HT2A receptor-induced suppression reported in previous studies (−21%29 and −67%31, dark blue stippled lines). d Same as (c) for the fluctuation-driven regime. e Left: Average excitatory (orange) and inhibitory (blue) conductance predicted by the model with no 5-HT2A activation (0%) and during systemic 5-HT2A receptor activation in 50% of all cells (please note the different Y scales). Visual stimulation time is indicated by the black bar, blue marks receptor activation. Right: Firing rate with no 5-HT2A stimulation (0%) and during systemic 5-HT2A activation in 50% of all cells. Note that the increase in conductance following 5-HT2A activation leads to suppression of the response to visual input without changes in spontaneous firing rate. Source data are provided as a Source Data file.
