Whole Brain Mapping Of Afferent Input To Subdomain Accumbens Nucleus Core And Subneuclei Of Accumbens Nucleus

Background:Mapping the neural pathways of specific brain regions at the whole brain level is critical for understanding complex functions and brain diseases.The nucleus accumbens(NAc)on the ventral side of the striatum is generally considered to be the interface between cognition,emotion,and motion.NAcis an important part of the basal ganglia and is involved in many important brain functions(such as spatial navigation,reward processing,etc.),and is closely related to the occurrence of many mental and neurological diseases(such as depression,epilepsy,Alzheimer's disease,etc.).NAcconsists of three major subnuclei: NAccore(NAcC),lateral shell(NAcLS)and medial shell(NAcMS).Numerous studies have shown that different subregions of NAcmediate distinct functions in many behavioral paradigms.However,the functional basis of neural circuits that mediate functional differences in different subregions is not clear.The identification of direct upstream inputs to different subregions of NAchelps to understand the circuit mechanisms involved in different functions of NAc,and the revealing of these functional mechanisms is a necessary prerequisite for the analysis of the role of NAcin disease.Methods:1.Ten mice were divided into two groups and injected with cholera toxin B(CTB)with different fluorescent labels in the whole brain retrograde tracer in the subregions ofNAcC,i.e.,rostral,caudal,dorsal,and ventral subregions(rNAcC,cNAcC,dNAcCand vNAcC)and NAcshell(NAcS).2.Scan whole brain slices with automatic scanning system.After the scan,the brain slices were processed,and the neurons in the slices were manually labeled with Imag J to obtain the corresponding coordinates of the upstream input neurons in different brain regions.3.Coordinate information of processed brain slices and labeled neurons was loaded into the software package Whole Brain based on R language for whole-brain registration and analysis,and the distribution information of registered upstream neurons was obtained,so as to quantitatively compare the distribution of upstream neurons in different brain regions.Results:1.75 valid upstream brain regions projecting to NAc,and these diverse brain regions distributed from the cerebrum to brain stem.2.Of the 57 brain regions projecting toNAcC,the anterior olfactory nucleus(AON)contributed most of the afferent inputs toNAcC.The whole brain projecting distribution to to rNAcC and cNAcC is similar in projecting proportions but different neuron populations,while the projecting proportions to dNAcC and vNAcC is slightly different.3.Of the 72 brain regions projecting to NAcLS,the piriform area(PIR)contributed most of theafferent inputs.Of the 55 brain regions projecting to NAcMS,the lateral septal nucleus(LS)contributed most of the afferent inputs.Of the 75 regions included in the comparison,52 regions showed different projecting proportions to the NAcsubneuclei.NAcMS is more inclined to receive inputs from evolutionarily more conserved regions,while NAcC and NAcLS is more inclined to accept input from neocortex.The conclusion is that subdomains of NAcC share same upstream brain regions with different projecting neuron population or projecting proportions while subneuclei of NAcreceive distinct inputs from multiple upstream brain regions.Theseresults lay the anatomical foundation to understanding the afferent input pattern of NAcC subdomain and NAcsubnucleis and the functional differences among them.Conclusions:Using the Whole Brain framework for brain-wide maps,we can quantify the brain-wide distribution of input neurons of different brains and injection sites.We analyzed the input patterns of different subregions of NAccore and shell in each upstream brain region.Brain-wide input patterns of the NAcC subdomains most of which received inputs from different neuronal populations in the same upstream brain regions and with a little difference in proportion of projecting.Comparing the brain-wide input patterns of the NAcC and NAcS subnuclei,the NAcMS had distinct upstream brain regions from theNAcC as well as the NAcLS,whereas the NAcC and NAcLS had similar upstream brain regions but different distribution of input proportions across those regions.