Inhibitory Control of Prefrontal Cortex by the Claustrum

Jesse Jackson*, Mahesh M. Karnani, Boris V. Zemelman, Denis Burdakov, Albert K. Lee

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


The claustrum is a small subcortical nucleus that has extensive excitatory connections with many cortical areas. While the anatomical connectivity from the claustrum to the cortex has been studied intensively, the physiological effect and underlying circuit mechanisms of claustrocortical communication remain elusive. Here we show that the claustrum provides strong, widespread, and long-lasting feedforward inhibition of the prefrontal cortex (PFC) sufficient to silence ongoing neural activity. This claustrocortical feedforward inhibition was predominantly mediated by interneurons containing neuropeptide Y, and to a lesser extent those containing parvalbumin. Therefore, in contrast to other long-range excitatory inputs to the PFC, the claustrocortical pathway is designed to provide overall inhibition of cortical activity. This unique circuit organization allows the claustrum to rapidly and powerfully suppress cortical networks and suggests a distinct role for the claustrum in regulating cognitive processes in prefrontal circuits. The claustrum provides a dense synaptic input to the cortex, but how claustrocortical projections modulate cortical activity is not known. Jackson et al. show that claustrocortical connections serve to inhibit cortical neural networks by activating specific subtypes of cortical interneurons.

Original languageEnglish
Pages (from-to)1029-1039.e4
Issue number5
Publication statusPublished - 5 Sep 2018
Externally publishedYes


  • claustrum
  • feed-forward inhibition
  • microcircuit
  • neocortex
  • neurogliaform cell
  • NPY
  • prefrontal
  • PV
  • somatostatin interneuron
  • VIP


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