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. 2017 Apr 17;127(5):1618–1621. doi: 10.1172/JCI93918

Figure 1. Decreased indirect pathway function in mice lacking the SHANK3 scaffolding protein.

Figure 1

Schematic diagrams of the cortico–basal ganglia direct and indirect pathways in WT mice and mice lacking the SHANK3 postsynaptic scaffolding protein. In WT mice, cortical synaptic input to direct and indirect pathway MSNs helps to keep the appropriate balance of striatal output that determines which actions are allowed and which are suppressed. In mice lacking SHANKB, cortical input to indirect pathway MSNs is weakened, resulting in less synaptic excitation of these neurons and less GABAergic inhibitory output to the globus pallidus external segment (GPe). This results in greater GABAergic inhibition of GPe output to the substantia nigra pars reticulata (SNr), thus suppressing basal ganglia output. The net result of these circuit changes is impaired suppression of unwanted actions, excessive grooming in particular.