Whole Brain Monosynaptic Input of Distinct Neurons in the Globus Pallidus Externa.

OBJECTIVE: The globus pallidus externa (GPe) is involved in mediating physiological functions and contains two types of neurons: Forkhead box protein P2-expressing (GPe(FoxP2)) neurons which inhibit motor, and parvalbumin-expressing (GPe(PV)) neurons which improve motor. The functional complexity of the GPe, directly linked to its neuronal heterogeneity, necessitates exploring the neuroanatomical circuits of its distinct neuron types as a foundation for functional research. METHODS: In this study, we employed specific, modified rabies viruses and adeno-associated viruses to investigate the monosynaptic inputs of GPe(FoxP2) and GPe(PV) neurons. RESULTS: We found that the input projections to both types of neurons are widespread, including the cortex, subcortical structures, amygdala, thalamus, hypothalamus, and brainstem. These inputs exhibit significant similarity, with 49 nuclei simultaneously innervating both types of neurons. However, GPe(PV) neurons receive a lower proportion of inputs from the cortex and a higher proportion of inputs from the thalamus, compared to GPe(FoxP2) neurons. Clustering analysis indicates that GPe(FoxP2) neurons receive extensive afferent inputs from four nuclear clusters in the brain, whereas GPe(PV) neurons receive afferent inputs from only three clusters, suggesting GPe(FoxP2) neurons may be involved in more diverse functional regulations than GPe(PV). CONCLUSION: Collectively, our results reveal the similarities and differences in the input projections to the two types of neurons in the GPe and lay the neuroanatomic groundwork for further studies to explore the critical physiological functions of GPe.