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. 2016 Jun 6;126(7):2482–2494. doi: 10.1172/JCI85033

Figure 10. M1-AChR on SST interneurons mediates the rapid antidepressant response to scopolamine.

Figure 10

In the mPFC of WT mice, M1-AChR expression on SST-GABA interneurons is antagonized by scopolamine, leading to disinhibition of pyramidal glutamate (PYR-Glut) neurons, resulting in increased glutamate release. This causes activation of surrounding target pyramidal neurons and increased FosB expression. Importantly, this burst of glutamate also stimulates postsynaptic signaling pathways that increase synaptic number and function that ultimately underlie the rapid antidepressant actions of scopolamine. In the mPFC of Sst-Cre mice, M1-AChR knockdown on SST-GABA interneurons prevents scopolamine blockade of inhibitory input on pyramidal neurons. This lack of disinhibition or maintenance of GABA inhibition of PYR-Glut neurons prevents the glutamate burst and the downstream cellular and molecular pathways underlying the synaptic and antidepressant behavioral actions of scopolamine.