Anatomical Organization of the Extended Amygdala

The concept of the extended amygdala proposed by de Olmos and Heimer suggests that the central (CEA) and medial nuclei of the amygdala (MEA) and the bed nucleus of stria terminalis (BST) are parts of a contiguous cellular column of neurons with similar anatomical connectivity and functional output (Olmos; and Heimer; 1999). An alternative hypothesis proposed by Larry Swanson suggests that the CEA/MEA and BST are ventral differentiations of the striatum and pallidum, together forming a striatopallidal circuit that participates in a cortical reentrant loop (Swanson and Petrovich 1998, Swanson 2000). In support of the extended amygdala concept, connections between the amygdala and BST are topographically-organized, suggesting the presence of discrete channels for information processing. Furthermore, results from several studies indicate that lesions of the amygdala or BST often produce experimental results that are quite similar (Zardetto-Smith, Beltz et al. 1994, Newman 1999, Tanimoto, Nakagawa et al. 2003, Nakagawa, Yamamoto et al. 2005, Deyama, Nakagawa et al. 2007). On the other hand, the concept of the extended amygdala has been challenged by results from behavioral studies that suggest a dissociation of CEA and BST functions in mediating behavioral processes associated with fear, anxiety (Walker and Davis 1997, Fendt, Endres et al. 2003, Walker, Toufexis et al. 2003, Sullivan, Apergis et al. 2004), social defeat (Jasnow, Davis et al. 2004), social interaction (Cecchi, Khoshbouei et al. 2002) and ethanol self-administration (Funk, O'Dell et al. 2006). The studies in this dissertation were designed to test some of the assumptions proposed by the extended amygdala concept by more closely examining the similarities of extended amygdala circuits. In the first study, we tested the hypothesis proposed by de Olmos and Heimer that “all or most of the central extended amygdala would share similar inputs” (de Olmos and Heimer 1999). In the second study, we examined multisynaptic BST circuits that project to CEA and MEA to determine if BST circuits were maintained within topographically-organized channels. Our findings reveal several organizational principles for the anatomical relationship of the amygdala and BST subnuclei and suggest new theories for how extended amygdala circuits process information

Precise segmentation of densely interweaving neuron clusters using G-Cut

脑是宇宙间最为复杂的系统之一，成人的脑中有约1000亿个神经元，单个神经元通常与其它神经元有成千上万个“突触”连接节点，形成拥有百万亿级连接的极其复杂的脑神经网络。当前多数神经元三维重建和分析工具仅适用于单个神经元的形态学重建，难以从神经元簇图像中正确追踪重建出多个神经元，而神经元的重建质量又影响到量化分析神经元的形态学特征及其功能。针对这一问题，课题组提出一种新的三维神经元簇重建工具G-Cut。具体地，为了度量神经元胞体与神经突起间的关联性，课题组从已有的带有标注的大规模神经元形态学数据集统计分析得到其规律和形态学信息。然后将神经元簇的重建问题转化为神经突起之间连接所形成的拓扑连接图的图分割问题，并结合神经元形态学规律和信息，在所有的神经突起与神经元胞体的关联性中寻找重建问题的最优解。通过在不同的合成数据集以及真实的脑组织图像数据集上测试，和已有的方法相比，G-Cut在不同密度和不同规模的神经元簇图像上均获得了更高的重建正确率。该项研究工作由厦门大学，南加州大学，加州大学洛杉矶分校等高校课题组合作完成，厦门大学信息学院智能科学与技术系为第一完成单位，厦门大学博士生李睿和USC博士生Muye Zhu为论文共同第一作者，张俊松博士和南加州大学的Hong-Wei Dong教授为论文共同通讯作者。厦门大学周昌乐教授和南加州大学的Arthur Toga教授为研究提供了大力支持。【Abstract】Characterizing the precise three-dimensional morphology and anatomical context of neurons is crucial for neuronal cell type classification and circuitry mapping. Recent advances in tissue clearing techniques and microscopy make it possible to obtain image stacks of intact, interweaving neuron clusters in brain tissues. As most current 3D neuronal morphology reconstruction methods are only applicable to single neurons, it remains challenging to reconstruct these clusters digitally. To advance the state of the art beyond these challenges, we propose a fast and robust method named G-Cut that is able to automatically segment individual neurons from an interweaving neuron cluster. Across various densely interconnected neuron clusters, G-Cut achieves significantly higher accuracies than other state-of-the-art algorithms. G-Cut is intended as a robust component in a high throughput informatics pipeline for large-scale brain mapping projects.This work was supported by NIH/NIMH MH094360-01A1 (H.W.D.), MH094360-06 (H.W.D.), NIH/NCI U01CA198932-01 (H.W.D.), NIH/NIMH MH106008 (X.W.Y. and H.W.D.), National Nature Science Foundation of China No. 61772440 (J.S.Z.), and National Basic Research Program of China 2013CB329502 (J.S.Z. and C.L.Z.). We thank a support of Graduate Student International Exchange Project of Xiamen University to R.L. and State Scholarship Fund of China Scholarship Council (No. 201406315023) to J.S.Z. 该项研究得到国家自然科学基金、国家重点基础研究发展计划973项目、国家留学基金、厦门大学研究生国际交流项目、美国脑计划和NIH等课题资助

CD14 Deficiency Impacts Glucose Homeostasis in Mice through Altered Adrenal Tone

The toll-like receptors comprise one of the most conserved components of the innate immune system, signaling the presence of molecules of microbial origin. It has been proposed that signaling through TLR4, which requires CD14 to recognize bacterial lipopolysaccharide (LPS), may generate low-grade inflammation and thereby affect insulin sensitivity and glucose metabolism. To examine the long-term influence of partial innate immune signaling disruption on glucose homeostasis, we analyzed knockout mice deficient in CD14 backcrossed into the diabetes-prone C57BL6 background at 6 or 12 months of age. CD14-ko mice, fed either normal or high-fat diets, displayed significant glucose intolerance compared to wild type controls. They also displayed elevated norepinephrine urinary excretion and increased adrenal medullary volume, as well as an enhanced norepinephrine secretory response to insulin-induced hypoglycemia. These results point out a previously unappreciated crosstalk between innate immune- and sympathoadrenal- systems, which exerts a major long-term effect on glucose homeostasis

Cellular anatomy of the mouse primary motor cortex.

An essential step toward understanding brain function is to establish a structural framework with cellular resolution on which multi-scale datasets spanning molecules, cells, circuits and systems can be integrated and interpreted1. Here, as part of the collaborative Brain Initiative Cell Census Network (BICCN), we derive a comprehensive cell type-based anatomical description of one exemplar brain structure, the mouse primary motor cortex, upper limb area (MOp-ul). Using genetic and viral labelling, barcoded anatomy resolved by sequencing, single-neuron reconstruction, whole-brain imaging and cloud-based neuroinformatics tools, we delineated the MOp-ul in 3D and refined its sublaminar organization. We defined around two dozen projection neuron types in the MOp-ul and derived an input-output wiring diagram, which will facilitate future analyses of motor control circuitry across molecular, cellular and system levels. This work provides a roadmap towards a comprehensive cellular-resolution description of mammalian brain architecture

Automatic access of the meanings of ambiguous words in context : some limitations of knowledge-based processing

Bibliography: leaves 66-74Supported by a grant from the National Science Foundation IST 80-12439 , by the National Institute of Education under contract no. US-NIE-C-400-76-011

Connectivity characterization of the mouse basolateral amygdalar complex.

The basolateral amygdalar complex (BLA) is implicated in behaviors ranging from fear acquisition to addiction. Optogenetic methods have enabled the association of circuit-specific functions to uniquely connected BLA cell types. Thus, a systematic and detailed connectivity profile of BLA projection neurons to inform granular, cell type-specific interrogations is warranted. Here, we apply machine-learning based computational and informatics analysis techniques to the results of circuit-tracing experiments to create a foundational, comprehensive BLA connectivity map. The analyses identify three distinct domains within the anterior BLA (BLAa) that house target-specific projection neurons with distinguishable morphological features. We identify brain-wide targets of projection neurons in the three BLAa domains, as well as in the posterior BLA, ventral BLA, posterior basomedial, and lateral amygdalar nuclei. Inputs to each nucleus also are identified via retrograde tracing. The data suggests that connectionally unique, domain-specific BLAa neurons are associated with distinct behavior networks

Connectivity characterization of the mouse basolateral amygdalar complex.

The basolateral amygdalar complex (BLA) is implicated in behaviors ranging from fear acquisition to addiction. Optogenetic methods have enabled the association of circuit-specific functions to uniquely connected BLA cell types. Thus, a systematic and detailed connectivity profile of BLA projection neurons to inform granular, cell type-specific interrogations is warranted. Here, we apply machine-learning based computational and informatics analysis techniques to the results of circuit-tracing experiments to create a foundational, comprehensive BLA connectivity map. The analyses identify three distinct domains within the anterior BLA (BLAa) that house target-specific projection neurons with distinguishable morphological features. We identify brain-wide targets of projection neurons in the three BLAa domains, as well as in the posterior BLA, ventral BLA, posterior basomedial, and lateral amygdalar nuclei. Inputs to each nucleus also are identified via retrograde tracing. The data suggests that connectionally unique, domain-specific BLAa neurons are associated with distinct behavior networks

The mouse cortico-basal ganglia-thalamic network.

The cortico-basal ganglia-thalamo-cortical loop is one of the fundamental network motifs in the brain. Revealing its structural and functional organization is critical to understanding cognition, sensorimotor behaviour, and the natural history of many neurological and neuropsychiatric disorders. Classically, this network is conceptualized to contain three information channels: motor, limbic and associative1-4. Yet this three-channel view cannot explain the myriad functions of the basal ganglia. We previously subdivided the dorsal striatum into 29 functional domains on the basis of the topography of inputs from the entire cortex5. Here we map the multi-synaptic output pathways of these striatal domains through the globus pallidus external part (GPe), substantia nigra reticular part (SNr), thalamic nuclei and cortex. Accordingly, we identify 14 SNr and 36 GPe domains and a direct cortico-SNr projection. The striatonigral direct pathway displays a greater convergence of striatal inputs than the more parallel striatopallidal indirect pathway, although direct and indirect pathways originating from the same striatal domain ultimately converge onto the same postsynaptic SNr neurons. Following the SNr outputs, we delineate six domains in the parafascicular and ventromedial thalamic nuclei. Subsequently, we identify six parallel cortico-basal ganglia-thalamic subnetworks that sequentially transduce specific subsets of cortical information through every elemental node of the cortico-basal ganglia-thalamic loop. Thalamic domains relay this output back to the originating corticostriatal neurons of each subnetwork in a bona fide closed loop