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.
