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Proceedings of the National Academy of... Dec 2019Brain infection by the parasite in mice is thought to generate vulnerability to predation by mechanisms that remain elusive. Monocytes play a key role in host defense...
Brain infection by the parasite in mice is thought to generate vulnerability to predation by mechanisms that remain elusive. Monocytes play a key role in host defense and inflammation and are critical for controlling However, the dynamic and regional relationship between brain-infiltrating monocytes and parasites is unknown. We report the mobilization of inflammatory (CCR2Ly6C) and patrolling (CX3CR1Ly6C) monocytes into the blood and brain during infection of C57BL/6J and CCR2CX3CR1 mice. Longitudinal analysis of mice using 2-photon intravital imaging of the brain through cranial windows revealed that CCR2-RFP monocytes were recruited to the blood-brain barrier (BBB) within 2 wk of infection, exhibited distinct rolling and crawling behavior, and accumulated within the vessel lumen before entering the parenchyma. Optical clearing of intact -infected brains using iDISCO and light-sheet microscopy enabled global 3D detection of monocytes. Clusters of and individual monocytes across the brain were identified using an automated cell segmentation pipeline, and monocytes were found to be significantly correlated with sites of clusters. Computational alignment of brains to the Allen annotated reference atlas [E. S. Lein et al., 445:168-176 (2007)] indicated a consistent pattern of monocyte infiltration during infection to the olfactory tubercle, in contrast to LPS treatment of mice, which resulted in a diffuse distribution of monocytes across multiple brain regions. These data provide insights into the dynamics of monocyte recruitment to the BBB and the highly regionalized localization of monocytes in the brain during CNS infection.
Topics: Animals; Antigens, Ly; Blood-Brain Barrier; Brain; CX3C Chemokine Receptor 1; Disease Models, Animal; Female; Male; Mice; Mice, Inbred C57BL; Monocytes; Receptors, CCR2; Toxoplasmosis
PubMed: 31727842
DOI: 10.1073/pnas.1915778116 -
ENeuro 2019A fundamental strategy in sensory coding is parallel processing, whereby unique, distinct features of sensation are computed and projected to the central target in the...
A fundamental strategy in sensory coding is parallel processing, whereby unique, distinct features of sensation are computed and projected to the central target in the form of submodal maps. It remains unclear, however, whether such parallel processing strategy is employed in the main olfactory system, which codes the complex hierarchical odor and behavioral scenes. A potential scheme is that distinct subsets of projection neurons in the olfactory bulb (OB) form parallel projections to the targets. Taking advantage of the observation that the distinct projection neurons develop at different times, we developed a Cre-loxP-based method that allows for birthdate-specific labeling of cell bodies and their axon projections in mice. This birthdate tag analysis revealed that the mitral cells (MCs) born in an early developmental stage and the external tufted cells (TCs) born a few days later form segregated parallel projections. Specifically, the latter subset converges the axons onto only two small specific targets, one of which, located at the anterolateral edge of the olfactory tubercle (OT), excludes widespread MC projections. This target is made up of neurons that express dopamine D1 but not D2 receptor and corresponds to the most anterolateral isolation of the CAP compartments (aiCAP) that were defined previously. This finding of segregated projections suggests that olfactory sensing does indeed involve parallel processing of functionally distinct submodalities. Importantly, the birthdate tag method used here may pave the way for deciphering the functional meaning of these individual projection pathways in the future.
Topics: Animals; Mice; Mice, Transgenic; Neurons; Olfactory Bulb; Olfactory Pathways; Smell
PubMed: 31672846
DOI: 10.1523/ENEURO.0234-19.2019 -
Scientific Reports Oct 2019Hypoparathyroidism remains one of the most common complications in thyroid surgery. This study aims for an improved understanding of the complexity of the blood supply...
Hypoparathyroidism remains one of the most common complications in thyroid surgery. This study aims for an improved understanding of the complexity of the blood supply and the localisation of the parathyroids compared to the two most important intraoperative landmarks: the inferior laryngeal nerve (ILN) and Zuckerkandl's tubercle (ZT). We examined 103 laryngeal compounds to classify the blood supply and the localisation of the parathyroids. For intraoperative localisation we defined a Cartesian coordinate system with the ZT plane as x-axis and the course of the inferior laryngeal nerve as y-axis. The inferior thyroid artery (ITA) mainly supplies the parathyroids, whereas the superior thyroid artery provides a backup supply. It must be pointed out that 8.2% of parathyroids receive their blood directly from the thyroid gland. 73.5% of all parathyroids lie within 1 cm of the ILN and 1 cm cranial and 2.5 cm caudal to the ZT plane. Our described perimeters mark the most crucial areas during surgery and provide the surgeon with an anatomic mapping showing areas of special carefulness needed. One should keep bearing in mind all possible blood supply types of the parathyroids and therefore all branches should be handled with care.
Topics: Female; Humans; Hypoparathyroidism; Larynx; Male; Olfactory Tubercle; Parathyroid Glands; Postoperative Complications; Recurrent Laryngeal Nerve; Thyroid Gland; Thyroidectomy
PubMed: 31666619
DOI: 10.1038/s41598-019-52189-3 -
The Journal of Neuroscience : the... Nov 2019Sensory cortices process stimuli in manners essential for perception. Very little is known regarding interactions between olfactory cortices. The piriform "primary"...
Sensory cortices process stimuli in manners essential for perception. Very little is known regarding interactions between olfactory cortices. The piriform "primary" olfactory cortex, especially its anterior division (aPCX), extends dense association fibers into the ventral striatum's olfactory tubercle (OT), yet whether this corticostriatal pathway is capable of shaping OT activity, including odor-evoked activity, is unknown. Further unresolved is the synaptic circuitry and the spatial localization of OT-innervating PCX neurons. Here we build upon standing literature to provide some answers to these questions through studies in mice of both sexes. First, we recorded the activity of OT neurons in awake mice while optically stimulating principal neurons in the aPCX and/or their association fibers in the OT while the mice were delivered odors. This uncovered evidence that PCX input indeed influences OT unit activity. We then used patch-clamp recordings and viral tracing to determine the connectivity of aPCX neurons upon OT neurons expressing dopamine receptor types D1 or D2, two prominent cell populations in the OT. These investigations uncovered that both populations of neurons receive monosynaptic inputs from aPCX glutamatergic neurons. Interestingly, this input originates largely from the ventrocaudal aPCX. These results shed light on some of the basic physiological properties of this pathway and the cell-types involved and provide a foundation for future studies to identify, among other things, whether this pathway has implications for perception. Sensory cortices interact to process stimuli in manners considered essential for perception. Very little is known regarding interactions between olfactory cortices. The present study sheds light on some of the basic physiological properties of a particular intercortical pathway in the olfactory system and provides a foundation for future studies to identify, among other things, whether this pathway has implications for perception.
Topics: Animals; Female; Glutamic Acid; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Odorants; Olfactory Receptor Neurons; Olfactory Tubercle; Piriform Cortex; Receptors, Dopamine D1; Receptors, Dopamine D2; Smell
PubMed: 31628176
DOI: 10.1523/JNEUROSCI.1444-19.2019 -
ELife Jul 2019The central processing pathways of the human olfactory system are not fully understood. The olfactory bulb projects directly to a number of cortical brain structures,...
The central processing pathways of the human olfactory system are not fully understood. The olfactory bulb projects directly to a number of cortical brain structures, but the distinct networks formed by projections from each of these structures to the rest of the brain have not been well-defined. Here, we used functional magnetic resonance imaging and k-means clustering to parcellate human primary olfactory cortex into clusters based on whole-brain functional connectivity patterns. Resulting clusters accurately corresponded to anterior olfactory nucleus, olfactory tubercle, and frontal and temporal piriform cortices, suggesting dissociable whole-brain networks formed by the subregions of primary olfactory cortex. This result was replicated in an independent data set. We then characterized the unique functional connectivity profiles of each subregion, producing a map of the large-scale processing pathways of the human olfactory system. These results provide insight into the functional and anatomical organization of the human olfactory system.
Topics: Adult; Anatomy, Artistic; Atlases as Topic; Female; Humans; Male; Nerve Net; Olfactory Cortex; Olfactory Pathways
PubMed: 31339489
DOI: 10.7554/eLife.47177 -
Neuropeptides Aug 2019Neurotensin (Nts) is a neuropeptide implicated in the regulation of many facets of physiology, including cardiovascular tone, pain processing, ingestive behaviors,...
Neurotensin (Nts) is a neuropeptide implicated in the regulation of many facets of physiology, including cardiovascular tone, pain processing, ingestive behaviors, locomotor drive, sleep, addiction and social behaviors. Yet, there is incomplete understanding about how the various populations of Nts neurons distributed throughout the brain mediate such physiology. This knowledge gap largely stemmed from the inability to simultaneously identify Nts cell bodies and manipulate them . One means of overcoming this obstacle is to study mice crossed onto a Cre-inducible green fluorescent reporter line ( mice), as these mice permit both visualization and modulation of specific populations of Nts neurons (using Cre-inducible viral and genetic tools) to reveal their function. Here we provide a comprehensive characterization of the distribution and relative densities of the Nts-GFP populations observed throughout the male mouse brain, which will pave the way for future work to define their physiologic roles. We also compared the distribution of Nts-GFP neurons with - Hybridization (-ISH) data from the adult mouse brain. By comparing these data sets we can distinguish Nts-GFP populations that may only transiently express Nts during development but not in the mature brain, and hence which populations may not be amenable to Cre-mediated manipulation in adult mice. This atlas of Nts-GFP neurons will facilitate future studies using the line to describe the physiological functions of individual Nts populations and how modulating them may be useful to treat disease.
Topics: Animals; Atlases as Topic; Brain; Male; Mice, Inbred C57BL; Mice, Transgenic; Neurons; Neurotensin
PubMed: 31079844
DOI: 10.1016/j.npep.2019.05.001 -
Progress in Neurobiology Sep 2019In mammals, including humans, MTH1 with 8-oxo-dGTPase and OGG1 with 8-oxoguanine DNA glycosylase minimize 8-oxoguanine accumulation in genomic DNA. We investigated...
In mammals, including humans, MTH1 with 8-oxo-dGTPase and OGG1 with 8-oxoguanine DNA glycosylase minimize 8-oxoguanine accumulation in genomic DNA. We investigated age-related alterations in behavior, 8-oxoguanine levels, and neurogenesis in the brains of Mth1/Ogg1-double knockout (TO-DKO), Ogg1-knockout, and human MTH1-transgenic (hMTH1-Tg) mice. Spontaneous locomotor activity was significantly decreased in wild-type mice with age, and females consistently exhibited higher locomotor activity than males. This decrease was significantly suppressed in female but not male TO-DKO mice and markedly enhanced in female hMTH1-Tg mice. Long-term memory retrieval was impaired in middle-aged female TO-DKO mice. 8-Oxoguanine accumulation significantly increased in nuclear DNA, particularly in the dentate gyrus (DG), subventricular zone (SVZ) and major island of Calleja (ICjM) in middle-aged female TO-DKO mice. In middle-aged female TO-DKO mice, neurogenesis was severely impaired in SVZ and DG, accompanied by ICjM and DG atrophy. Conversely, expression of hMTH1 efficiently suppressed 8-oxoguanine accumulation in both SVZ and DG with hypertrophy of ICjM. These findings indicate that newborn neurons from SVZ maintain ICjM in the adult brain, and increased accumulation of 8-oxoguanine in nuclear DNA of neural progenitors in females is caused by 8-oxo-dGTP incorporation during proliferation, causing depletion of neural progenitors, altered behavior, and cognitive function changes with age.
Topics: Aging; Animals; Cell Proliferation; DNA Repair Enzymes; Dentate Gyrus; Female; Islands of Calleja; Mice, Transgenic; Neurogenesis; Neurons; Phenotype; Phosphoric Monoester Hydrolases; Sex Characteristics
PubMed: 31026482
DOI: 10.1016/j.pneurobio.2019.04.002