Knowledge about the neuronal dynamics and the projectome are both essential for understanding how the neuronal network functions in concert. However, it remains challenging to obtain the neural activity and the brain-wide projectome for the same neurons, especially for neurons in subcortical brain regions. Here, by combining in vivo microscopy and high-definition fluorescence micro-optical sectioning tomography, we have developed strategies for mapping the brain-wide projectome of functionally relevant neurons in the somatosensory cortex, the dorsal hippocampus, and the substantia nigra pars compacta. More importantly, we also developed a strategy to achieve acquiring the neural dynamic and brain-wide projectome of the molecularly defined neuronal subtype. The strategies developed in this study solved the essential problem of linking brain-wide projectome to neuronal dynamics for neurons in subcortical structures and provided valuable approaches for understanding how the brain is functionally organized via intricate connectivity patterns.
Animals ; Neurons/physiology* ; Mice ; Brain/physiology* ; Mice, Inbred C57BL ; Somatosensory Cortex/physiology* ; Neural Pathways/physiology* ; Hippocampus/physiology* ; Mice, Transgenic ; Male ; Brain Mapping ; Nerve Net/physiology* ; Substantia Nigra/physiology* ; Tomography, Optical/methods*

Neurons in the primary auditory area (AUDp) innervate multiple brain regions with long-range projections while receiving informative inputs for diverse functions. However, the brain-wide connections of these neurons have not been comprehensively investigated. Here, we simultaneously applied virus-based anterograde and retrograde tracing, labeled the connections of excitatory and inhibitory neurons in the mouse AUDp, and acquired whole-brain information using a dual-channel fluorescence micro-optical sectioning tomography system. Quantified results showed that the two types of neurons received inputs with similar patterns but sent heterogeneous projections to downstream regions. In the isocortex, functionally different areas consistently sent feedback-dominated projections to these neurons, with concomitant laterally-dominated projections from the sensory and limbic cortices to inhibitory neurons. In subcortical regions, the dorsal and medial parts of the non-lemniscal auditory thalamus (AT) were reciprocally connected to the AUDp, while the ventral part contained the most fibers of passage from the excitatory neurons and barely sent projections back, indicating the regional heterogeneity of the AUDp-AT circuit. Our results reveal details of the whole-brain network and provide new insights for further physiological and functional studies of the AUDp.

Many people affected by fragile X syndrome (FXS) and autism spectrum disorders have sensory processing deficits, such as hypersensitivity to auditory, tactile, and visual stimuli. Like FXS in humans, loss of Fmr1 in rodents also cause sensory, behavioral, and cognitive deficits. However, the neural mechanisms underlying sensory impairment, especially vision impairment, remain unclear. It remains elusive whether the visual processing deficits originate from corrupted inputs, impaired perception in the primary sensory cortex, or altered integration in the higher cortex, and there is no effective treatment. In this study, we used a genetic knockout mouse model (Fmr1^KO), in vivo imaging, and behavioral measurements to show that the loss of Fmr1 impaired signal processing in the primary visual cortex (V1). Specifically, Fmr1^KO mice showed enhanced responses to low-intensity stimuli but normal responses to high-intensity stimuli. This abnormality was accompanied by enhancements in local network connectivity in V1 microcircuits and increased dendritic complexity of V1 neurons. These effects were ameliorated by the acute application of GABA_A receptor activators, which enhanced the activity of inhibitory neurons, or by reintroducing Fmr1 gene expression in knockout V1 neurons in both juvenile and young-adult mice. Overall, V1 plays an important role in the visual abnormalities of Fmr1^KO mice and it could be possible to rescue the sensory disturbances in developed FXS and autism patients.
Animals ; Disease Models, Animal ; Fragile X Mental Retardation Protein/metabolism* ; Fragile X Syndrome/metabolism* ; Humans ; Mice ; Mice, Knockout ; Neurons/metabolism*

The caudal forelimb area (CFA) of the mouse cortex is essential in many forelimb movements, and diverse types of GABAergic interneuron in the CFA are distinct in the mediation of cortical inhibition in motor information processing. However, their long-range inputs remain unclear. In the present study, we combined the monosynaptic rabies virus system with Cre driver mouse lines to generate a whole-brain map of the inputs to three major inhibitory interneuron types in the CFA. We discovered that each type was innervated by the same upstream areas, but there were quantitative differences in the inputs from the cortex, thalamus, and pallidum. Comparing the locations of the interneurons in two sub-regions of the CFA, we discovered that their long-range inputs were remarkably different in distribution and proportion. This whole-brain mapping indicates the existence of parallel pathway organization in the forelimb subnetwork and provides insight into the inhibitory processes in forelimb movement to reveal the structural architecture underlying the functions of the CFA.

Objective To investigate the effect of glutamine on the serum carcino embryonie antigen (CEA) , alpha fetal protein (AFP) and T cell immune function in postoperative patients with gastric cancer.Methods 52 postoperative patients with gastric cancer from Yiwu Central Hospital were selected and randomly divided into control group and experimenal group, 26 cases in each group.The control group received routine nutritional therapy, and experimental group received alanyl -glutamine injection on the basis of control group.The serum nutritional parameters, CEA, AFP, CD4 +T, CD8 +T levels were compared post-treatment.Results Compared with control group post-treatment, the serum albumin (ALB) and pre-albumin (PA) levels were higher (P<0.05), the CEA and AFP levels were lower (P<0.05),the serum levels of CD4 +T and CD4 +T/CD8 +T were higher (P<0.05),CD8 +T level were lower (P<0.05).Conclusion Glutamine could significantly improve the clinical symptoms of patients with gastric cancer after surgery,and it is speculated that the mechanism may be the increase of serum ALB, PA levels, the decrease of CEA, AFP levels and the improvement of immune function.

Objective To analyse effect of ShenQi FuZheng injection on serum carbohydrate antigen 19-9(CA19-9), C-reaction protein(CRP) and CD4 +lymphocyte subsets in patients after laparoscopic radical resection of colon cancer.Methods 58 patients after laparoscopic radical resection of colon cancer were collected.All patients were randomly divided into experimental group and control group according to the different drugs, 29 cases in each group.Patients were given the corresponding drug treatment after operation, after the treatment, the serum levels of CA19-9, CRP and venous blood T lymphocyte level were detected in all patients.Results Compared with before treatment, CA19-9 and CRP level in serum were lower (P<0.05) , CD4 +cells, CD4 +/CD8 +, and NK cells were higher(P<0.05);Compared with control group after treatment, the serum CA19-9 and CRP level were lower in the experimental group (P<0.05); the levels of venousblood CD4 +cells, CD4 +/CD8 +and NK cells were higher in the experimental group (P<0.05).Conclusion ShenQi FuZheng injection can significantly reduce the serum CRP and CA19-9 levels in patients after laparoscopic radical resection of colon cancer, improve the levels of venous blood CD4 +cells, CD4 +/CD8 +and NK cells, improve immune function, and have a guiding significance for clinica.