Whole-Brain Monosynaptic Inputs to and Axonal Projections From Posterior Insular Cortex GABAergic Neurons in Mice.

BACKGROUND: The posterior insular cortex (PIC) is a multimodal sensory integration center, and the GABAergic neurons are associated with functions such as pain perception, emotional regulation, and fear memories encoding. However, the whole-brain connectivity to PIC GABAergic neurons remains unclear. OBJECTIVE: To map the whole-brain input-output connectivity of PIC GABAergic neurons. METHODS: This study combined cell-type-specific retrograde/anterograde viral tracing systems with Cre/loxP genetic technology to perform a comparative analysis of the localization and quantification of monosynaptic inputs and axonal projections of PIC GABAergic neurons. RESULTS: Retrograde tracing identified 45 input nuclei, with densest inputs from the piriform cortex (Pir) and secondary somatosensory cortex (S2) of the isocortex, thalamic nuclei including the posterior thalamic nuclear group (PO) and parafascicular thalamic (PAF), exhibiting ipsilateral preference. Anterograde tracing revealed 18 output targets, with densest projections to the caudate putamen (CPu), external globus pallidus (GPe), and ventral pallidum (VP) of the basal ganglia and multiple subnuclei of the amygdala. CONCLUSIONS: PIC GABAergic neurons receive dense inputs from the isocortex and thalamus and send prominent projections to the basal ganglia and amygdala, with these brain regions constituting key hubs of the whole-brain connectivity network. This connectivity pattern provides a novel anatomical perspective for elucidating their roles in physiological behavior regulation.