Inhibitory Control of Prefrontal Cortex by the Claustrum

• Published in: Neuron (Cambridge, Mass.) Vol. 99; no. 5; pp. 1029 - 1039.e4
• Main Authors: Jackson, Jesse, Karnani, Mahesh M., Zemelman, Boris V., Burdakov, Denis, Lee, Albert K.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.09.2018; Elsevier Limited; Cell Press
• Subjects: Animals; Basal ganglia; Basal Ganglia - chemistry; Basal Ganglia - physiology; Brain research; claustrum; Cognitive ability; Crick, Francis; feed-forward inhibition; Female; Funding; Interneurons; Male; Medical research; Mice; Mice, Inbred C57BL; Mice, Transgenic; microcircuit; neocortex; Neural Inhibition - physiology; Neural networks; Neural Pathways - chemistry; Neural Pathways - physiology; neurogliaform cell; Neurons; Neuropeptide Y; NPY; Organ Culture Techniques; Parvalbumin; prefrontal; Prefrontal cortex; Prefrontal Cortex - chemistry; Prefrontal Cortex - physiology; Rats; Rats, Long-Evans; somatostatin interneuron; VIP; United Kingdom > UK; neurogliaform cell; feed-forward inhibition; somatostatin interneuron; prefrontal; NPY; PV; claustrum; neocortex; microcircuit; VIP
• ISSN: 0896-6273; 1097-4199; 1097-4199
• DOI: 10.1016/j.neuron.2018.07.031

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. [Display omitted] •The claustrum strongly inhibits, rather than excites, prefrontal cortex•Prefrontal NPY and PV interneurons are activated by the claustrum•Claustrocortical feedforward inhibition is predominantly mediated by NPY neurons 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.