Recurrent rewiring of the adult hippocampal mossy fiber system by a single transcriptional regulator, Id2

Circuit formation in the central nervous system has been historically studied during development, after which cell-autonomous and nonautonomous wiring factors inactivate. In principle, balanced reactivation of such factors could enable further wiring in adults, but their relative contributions may be circuit dependent and are largely unknown. Here, we investigated hippocampal mossy fiber sprouting to gain insight into wiring mechanisms in mature circuits. We found that sole ectopic expression of Id2 in granule cells is capable of driving mossy fiber sprouting in healthy adult mouse and rat. Mice with the new mossy fiber circuit solved spatial problems equally well as controls but appeared to rely on local rather than global spatial cues. Our results demonstrate reprogrammed connectivity in mature neurons by one defined factor and an assembly of a new synaptic circuit in adult brain. Overall design: To characterize single-cell transcriptome of GCs after chemical induction (70 nl 5 mM kainic acid, KA, microinjection into the hippocampus), patch-RNAseq was used to sample single dentate GCs for their transcriptomic content 1 and 14 days after KA microinjection. Partitioning of the data is as follows: (1) 1 day after KA: KA1_DG_ipsi, 63 cells; (2) 14 days after KA: Kainate_DG, 29 cells; (3) Control cells collected from non-injected mice: DG, 42 cells. To characterize single-cell transcriptome of GCs after AAV-gene overexpression, patch-RNAseq was used to sample single dentate GCs for their transcriptomic content 1 month after AAV injection. Partitioning of the data is as follows: (1) GFP overexpression as controls: GFP_Control, 70 cells; (2) Id2 overexpression: Id2_OE, 95 cells.