Pyramidal cell types and circuit organization of the mouse insular cortex reveal functional specializations

The insular cortex integrates interoceptive and exteroceptive information to mediate bodily homeostasis, emotion and learning. However, the cellular and circuit substrates governing insular functions are poorly understood compared to primary cortices. Here we quantify dendritic morphology together with projections, electrical properties and/or local inputs of 1,130 mouse insular pyramidal neurons. Neurons are mapped onto a quantitative Nissl-derived model of the insula. Using improved algorithms, we define 21 morphological, 12 electrical and 9 input neuronal types, some unique to the insula. Several types exhibit elaborate dendrites, reminiscent of primate cortical neurons. Furthermore, morphological properties constrain and often predict inputs, electrical properties, projection targets or molecular markers. Eight morphological types are differentially distributed between the functionally distinct anterior and posterior insula, facilitating a quantitative demarcation between these subregions. Certain types receive intra-insular excitatory inputs originating far beyond cortical columns, which functionally bridge a long-range thalamus-to-amygdala circuit linking sensory information to valence behaviorally. Our work establishes a structure-and-function foundation for investigating the insula.