Cux1 Enables Interhemispheric Connections of Layer II/III Neurons by Regulating Kv1-Dependent Firing Articles uri icon

authors

  • RODRÍGUEZ TORNOS, FERNANDA M.
  • BRIZ, CARLOS G.
  • WEISS, LINNEA A.
  • SEBASTIAN SERRANO, ÁLVARO
  • ARES GARCIA, SAUL
  • NAVARRETE, MARTA
  • FRANGEUL, LAURA
  • GALAZO, MARÍA
  • JABAUDON, DENIS
  • ESTEBAN, JOSÉ A.
  • NIETO, MARTA

published in

publication date

  • February 2016

start page

  • 494

end page

  • 506

issue

  • 3

volume

  • 89

International Standard Serial Number (ISSN)

  • 0896-6273

Electronic International Standard Serial Number (EISSN)

  • 1097-4199

abstract

  • Neuronal subtype-specific transcription factors (TFs) instruct key features of neuronal function and connectivity. Activity-dependent mechanisms also contribute to wiring and circuit assembly, but whether and how they relate to TF-directed neuronal differentiation is poorly investigated. Here we demonstrate that the TF Cux1 controls the formation of the layer II/III corpus callosum (CC) projections through the developmental transcriptional regulation of Kv1 voltage-dependent potassium channels and the resulting postnatal switch to a Kv1-dependent firing mode. Loss of Cux1 function led to a decrease in the expression of Kv1 transcripts, aberrant firing responses, and selective loss of CC contralateral innervation. Firing and innervation were rescued by re-expression of Kv1 or postnatal reactivation of Cux1. Knocking down Kv1 mimicked Cux1-mediated CC axonal loss. These findings reveal that activity-dependent processes are central bona fide components of neuronal TF-differentiation programs and establish the importance of intrinsic firing modes in circuit assembly within the neocortex.

keywords

  • callosal projection neurons; autism spectrum disorder; axon initial segment; in-vivo; cerebral-cortex; somatosensory cortex; cortical-neurons; expression; mouse; stimulation