Layer 1 NDNF interneurons are specialized top-down master regulators of cortical circuits

Cell Rep. 2024 May 28;43(5):114212. doi: 10.1016/j.celrep.2024.114212. Epub 2024 May 13.

Abstract

Diverse types of inhibitory interneurons (INs) impart computational power and flexibility to neocortical circuits. Whereas markers for different IN types in cortical layers 2-6 (L2-L6) have been instrumental for generating a wealth of functional insights, only the recent identification of a selective marker (neuron-derived neurotrophic factor [NDNF]) has opened comparable opportunities for INs in L1 (L1INs). However, at present we know very little about the connectivity of NDNF L1INs with other IN types, their input-output conversion, and the existence of potential NDNF L1IN subtypes. Here, we report pervasive inhibition of L2/3 INs (including parvalbumin INs and vasoactive intestinal peptide INs) by NDNF L1INs. Intersectional genetics revealed similar physiology and connectivity in the NDNF L1IN subpopulation co-expressing neuropeptide Y. Finally, NDNF L1INs prominently and selectively engage in persistent firing, a physiological hallmark disconnecting their output from the current input. Collectively, our work therefore identifies NDNF L1INs as specialized master regulators of superficial neocortex according to their pervasive top-down afferents.

Keywords: CP: Neuroscience; NDNF; PV; SST; VIP; circuit connectivity; interneurons; layer 1; neocortex; persistent firing; top-down information.

MeSH terms

  • Animals
  • Interneurons* / metabolism
  • Male
  • Mice
  • Neocortex / cytology
  • Neocortex / metabolism
  • Neocortex / physiology
  • Neuropeptide Y / metabolism
  • Parvalbumins / metabolism
  • Vasoactive Intestinal Peptide / metabolism

Substances

  • Neuropeptide Y
  • Vasoactive Intestinal Peptide
  • Parvalbumins