Diagramatic representation of effects of rapamycin treatment on dentate gyrus circuitry after focal brain injury. Diagramatic representation of effects.

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Diagramatic representation of effects of rapamycin treatment on dentate gyrus circuitry after focal brain injury. Diagramatic representation of effects of rapamycin treatment on dentate gyrus circuitry after focal brain injury. A, Normal circuit in dentate gyrus. The projection of a DGC onto a CA3 pyramidal cell is shown (solid black arrow). GABAergic hilar inhibitory interneurons are also present, but are not robustly innervated by DGCs or CA3 pyramidal cells (dashed arrows). B, Functional synaptic input to surviving hilar interneurons arising from activity in both DGCs and CA3 pyramidal cells (red arrows) are increased ipsilateral to CCI injury, as are connections between DGCs (red oval; Hunt et al., 2010, 2011; Butler et al., 2015). C, mTOR inhibition after CCI injury reduces reorganization of functional DGC connections with surviving hilar inhibitory interneurons, but aberrant excitatory connection arising from CA3 pyramidal cell activity is sustained. This cartoon does not discriminate between mono- and polysynaptic connections. Line thickness is used as a surrogate marker for the percentage effective stimulation sites as assessed by glutamate photolysis here and in Hunt et al. (2010). Corwin R. Butler et al. eNeuro 2017;4:ENEURO.0134-17.2017 ©2017 by Society for Neuroscience