• The Claustrum: From Top to Bottom

      White, Michael; Mathur, Brian N. (Brian Neil); 0000-0002-7202-7515 (2018)
      Despite much speculation, the function of the claustrum, a thin telencephalic brain nucleus, remains largely unknown. The claustrum is reciprocally connected with seemingly the entire cortical mantle, which motivates hypotheses of claustrum function that include multi-sensory integration and top-down/bottom-up attention. In order to discriminate these hypotheses, we examined the claustrum at multiple levels of analysis in rodents. We find that the claustrum is well-connected with executive areas of cortex, such as anterior cingulate cortex (ACC), and highly responsive to stimulation of ACC inputs in acute brain slices. In contrast, claustrum exhibits less connectivity with and responsivity to inputs from hierarchically lower cortices. Using in vivo circuit monitoring and manipulation, we find that ACC inputs to claustrum and claustrum projection neurons mediate top-down cognitive control relative to other basic brain functions, such as motor control and stimulus-response action strategy. Consistent with a role in cognitive control, claustrum neurons projecting to visual cortices and parietal association cortex faithfully propagate ACC input, and claustrum afferents provide strong excitatory drive across cortical layers. To understand how claustrum processes top-down input, we identified claustrum neuron subtypes using membrane properties and examined claustrum microcircuit responsivity to ACC input. We find that one of two claustrum projection neuron subtypes preferentially burst fires in response to ACC input, that the two subtypes differentially target cortex, and that recruitment of inhibitory microcircuits constrains claustrum output. These findings support a model wherein claustrum mediates synchronization of cortices for cognitive control.