title: Instructing Perisomatic Inhibition by Direct Lineage Reprogramming of Neocortical Projection Neurons.
abstract: During development of the cerebral cortex, local GABAergic interneurons recognize and pair with excitatory projection neurons to ensure the fine excitatory-inhibitory balance essential for proper circuit function. Whether the class-specific identity of projection neurons has a role in the establishment of afferent inhibitory synapses is debated. Here, we report that direct in vivo lineage reprogramming of layer 2/3 (L2/3) callosal projection neurons (CPNs) into induced corticofugal projection neurons (iCFuPNs) increases inhibitory input onto the converted neurons to levels similar to that of endogenous CFuPNs normally found in layer 5 (L5). iCFuPNs recruit increased numbers of inhibitory perisomatic synapses from parvalbumin (PV)-positive interneurons, with single-cell precision and despite their ectopic location in L2/3. The data show that individual reprogrammed excitatory projection neurons extrinsically modulate afferent input by local PV(+) interneurons, suggesting that projection neuron class-specific identity can actively control the wiring of the cortical microcircuit.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA; Center for Brain Science, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Zhanlei
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Mostajo-Radji
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Juliana R
authors.initials: JR
authors.lastname: Brown
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Rouaux
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Giulio Srubek
authors.initials: GS
authors.lastname: Tomassy
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA; Center for Brain Science, Harvard University, Cambridge, MA 02138, USA. Electronic address: hensch@mcb.harvard.edu.
authors.forename: Takao K
authors.initials: TK
authors.lastname: Hensch
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: paola_arlotta@harvard.edu.
authors.forename: Paola
authors.initials: P
authors.lastname: Arlotta
mesh_terms: D000818:Animals; D003337:Corpus Callosum / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D019579:Neocortex / Q000166:cytology / Q000502:physiology*; D009415:Nerve Net / Q000166:cytology / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology*; D009434:Neural Pathways / Q000166:cytology / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D009924:Organ Culture Techniques