Cell-Type-Specific Whole-Brain Afferent Innervation Of Different Nucleus Accumbens Subregions

Mapping the neural circuits of specific types of neurons in specific brain regions at the whole brain level is essential for understanding complex brain functions and brain diseases.As an important component of the basal ganglia,the nucleus accumbens?NAc?is clearly implicated in many important brain functions?such as reward processing,space navigation,etc.?,as well as in numerous neurological and psychiatric disorders?such as depression,Parkinson's disease,etc.?.Elucidating the neural circuit of NAc is a necessary prerequisite for revealing these functional mechanisms and disease mechanisms.The NAc,however,is an inhomogeneous tissue that is often divided into two primary segments:the shell and the core.The projection neurons within the NAc are GABAergic medium spiny neurons?MSNs?,which are dichotomized based on their expression of either D1 or D2 dopamine receptors.A large number of studies have shown that different types of neurons in different subregions of NAc mediate distinct functions in many behavioral paradigms.However,the circuitry mediating these functions remain poorly characterized.Therefore,to reveal the corresponding relationship between specific pathways and related functions,and provide accurate reference information for analyzing complex NAc functions,it is necessary to quantitatively analyze and compare the upstream and downstream pathways of specific types of neurons in different NAc subregions.In our study,we utilized a variety of neurotropic virus tools,combined with the recently developed rabies-virus-based transsynaptic retrograde tracing and TRIO labeling strategy,to systematically characterize the whole-brain and monosynaptic inputs to D1R-MSNs and D1R-MSNs in different NAc subregions,and to BL neurons projecting to different NAc subregions.The results of this study show that:?1?Our data showed an extremely high degree of overall similarity between inputs to D1R-MSNs and D2RMSNs in both NAc subregions.However,the input patterns to different NAc subregions differ significantly.Inputs to the NAc core are broadly scattered,whereas inputs to the NAc shell are relatively concentrated.Through quantitative comparisons,we identified numerous brain areas providing important contrasting inputs to different NAc subregions.The anterior cortex preferentially innervates the NAc core for both D1R-MSNs and D2R-MSNs,whereas the lateral hypothalamic area?LH?preferentially targets D1R-MSNs in the NAc shell.?2?Using the RVs expressing different fluorescent proteins to simultaneously label the inputs of the NAc core and the NAc shell in the same sample,we discovered that BL neurons projecting to different NAc subregions are anatomically distinct subpopulations(BL_core and BL_shell neuron).The whole brain input of BL_core and BL_shell neurons was analyzed by the TRIO labeling strategy.The results showed that BL_core and BL_shell neurons receive similar inputs from diverse sources.In summary,using a series of neurotropic virus tools combined with multiple viral labeling strategies,we first performed whole-brain mapping of both inputs to D1R-MSNs and D2R-MSNs in different NAc subregions and inputs to BL neurons projecting to different NAc subregions.This study lays a solid foundation for functional dissection of the neural circuitry of NAc and BL-NAc.