FIGURE 3.

The effects of neuromodulation on the depth of attractor states and synaptic plasticity. (A) As neural populations receive higher bouts of 5-HT_1A/B receptor activity and/or increased DA_2–4 receptor activity, the depth of an attractor state decreases. As neural populations experience higher levels of DA_1/5 receptor activity and/or increased levels of 5-HT_2A receptor activity, the depth of an attractor state increases. (B) Variable release of neuromodulation across time after receiving a given stimulus. DA (blue) and NE (yellow) exhibit short encoding of stimulus. 5-HT (pink) imposes a slower, sustained release onto synapses. (C) In healthy mPFC synapses, 5-HT_2A receptors (pink), D1-like receptors (dark blue), and AMPARs (red) interact to encourage NMDAR externalization. These receptors additionally recruit glutamatergic neurons (red). D2-like receptors (blue) internalize surface NMDARs and recruit GABAergic neurons (orange). Under unhealthy conditions in the mPFC, increased pressure from 5-HT_2A and D2-like receptors (in addition to decreased pressure from D1-like receptors) causes increased externalization of NMDARs and glutamatergic neuron recruitment. The consequence of this synaptic change is an excitatory/inhibitory imbalance in the mPFC. Abbreviations: 5-HT, serotonin; AMPAR, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptor; DA, dopamine, E, excitation; GABA, gamma-aminobutyric acid; I, inhibition; mPFC, medial prefrontal cortex; NE, norepinephrine; NMDAR, N-methyl-D-aspartate receptor; POST, postsynaptic neuron; PRE, presynaptic neuron.