The Synaptic Organization of Layer 6 Circuits Reveals Inhibition as a Major Output of a Neocortical Sublamina

Cell Rep. 2019 Sep 17;28(12):3131-3143.e5. doi: 10.1016/j.celrep.2019.08.048.


The canonical cortical microcircuit has principally been defined by interlaminar excitatory connections among the six layers of the neocortex. However, excitatory neurons in layer 6 (L6), a layer whose functional organization is poorly understood, form relatively rare synaptic connections with other cortical excitatory neurons. Here, we show that the vast majority of parvalbumin inhibitory neurons in a sublamina within L6 send axons through the cortical layers toward the pia. These interlaminar inhibitory neurons receive local synaptic inputs from both major types of L6 excitatory neurons and receive stronger input from thalamocortical afferents than do neighboring pyramidal neurons. The distribution of these interlaminar interneurons and their synaptic connectivity further support a functional subdivision within the standard six layers of the cortex. Positioned to integrate local and long-distance inputs in this sublayer, these interneurons generate an inhibitory interlaminar output. These findings call for a revision to the canonical cortical microcircuit.

Keywords: corticocortical neurons; corticothalamic neurons; fast-spiking interneurons; layer 6; neocortex; parvalbumin interneurons; thalamus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Interneurons / cytology
  • Interneurons / metabolism*
  • Mice
  • Mice, Transgenic
  • Neocortex / cytology
  • Neocortex / metabolism*
  • Neural Inhibition*
  • Pyramidal Cells / cytology
  • Pyramidal Cells / metabolism*
  • Synapses / genetics
  • Synapses / metabolism*