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In the dorsal lateral geniculate nucleus (LGN) of mice that lack retinal input, a population of large terminals supplants the synaptic arrangements normally made by the missing retinogeniculate terminals. To identify potential sources of these "retinogeniculate replacement terminals," we used mutant mice (math5

The ventral lateral geniculate nucleus (vLGN) is a retinorecipient region of thalamus that contributes to a num-ber of complex visual behaviors. Retinal axons that target vLGN terminate exclusively in the external subdivi-sion (vLGNe), which is also transcriptionally and cytoarchitectonically distinct from the internal subdivision (vLGNi). While recent studies shed light on the cell types and efferent projections of vLGNe and vLGNi, we have a crude understanding of the source and nature of the excitatory inputs driving postsynaptic activity in these regions. Here, we address this by conducting in vitro whole-cell recordings in acutely prepared thalamic slices and using electrical and optical stimulation techniques to examine the postsynaptic excitatory activity evoked by the activation of retinal or cortical layer V input onto neurons in vLGNe and vLGNi. Activation of ret-inal afferents by electrical stimulation of optic tract or optical stimulation of retinal terminals resulted in robust driver-like excitatory activity in vLGNe. Optical activation of corticothalamic terminals from layer V resulted in similar driver-like activity in both vLGNe and vLGNi. Using a dual-color optogenetic approach, we found that many vLGNe neurons received convergent input from these two sources. Both individual pathways displayed similar driver-like properties, with corticothalamic stimulation leading to a stronger form of synaptic depression than retinogeniculate stimulation. We found no evidence of convergence in vLGNi, with neurons only respond-ing to corticothalamic stimulation. These data provide insight into the influence of excitatory inputs to vLGN and reveal that only neurons in vLGNe receive convergent input from both sources.Significance StatementThe ventral lateral geniculate nucleus is traditionally thought of as a thalamic visual recipient structure. However, recent studies reveal its divergent output to a variety of nonvisual subcortical structures helps control an array of light-mediated defensive and mood-related behaviors. Despite this knowledge, we still lack an understanding of where and how inputs to this nucleus drive activity. Here we show that vLGN re-ceives strong, driver-like excitatory input from two sources: the retina and cortical layer V. The external sub-division receives convergent input from both sources, whereas the internal division receives input only from layer V. Such an arrangement has important implications for understanding the functional organization of vLGN and its role in integrating vision with internal behavioral states. Department of Health and Human Services | National Institutes of Health | National Eye Institute [EY-012716, EY-021222] Published version This work was supported by Department of Health and Human Services | National Institutes of Health | National Eye Institute Grants EY-012716 (to W. G.) and EY-021222 (to M.A.F.) .

During development, retinal axons create broad and imprecise connections in the thalamus. This topology, very different from adults, supplies developing thalamic neurons with locally homogeneous synaptic currents and should cause spike correlation between thalamocortical neurons on a millisecond timescale. Such correlations have not been observedin vivo, at these ages, and would likely be maladaptive. Here, we use a biophysical model of the visual thalamus with the membrane and synaptic properties of 7-10 day-old mice to show that the developmentally appropriate dominance of NMDA-receptor currents and absence of strong recurrent inhibitory and excitatory connections prevents precise correlation and preserves topographic information in thalamic spikes. We illustrate possible reasons for this desynchronization using a phenomenological cortical model, which shows impaired network diversity when driven with precisely correlated inputs. Our results suggest that developing synapses and circuits evolved mechanisms to compensate for detrimental, “parasitic” correlation arising from the unrefined and immature circuit.

Subpopulations of neurons and associated neural circuits can be targeted in mice with genetic tools in a highly selective manner for visualization and manipulation. However, there are not well-defined Cre 'driver' lines that target expression of Cre recombinase to thalamocortical neurons. Here were characterize three Cre driver lines for the nuclei of the dorsal thalamus: Oligodendrocyte transcription factor 3 (Olig3)-Cre, histidine decarboxylase (HDC)-Cre, and corticotropin-releasing hormone (CRH)-Cre. We examined the postnatal distribution of Cre expression for each of these lines with the Cre-dependent reporter CAG-tdTomato (Ai9). Cre-dependent expression of tdTomato reveals that Olig3-Cre expresses broadly within thalamus, including thalamocortical neurons and interneurons, while HDC-Cre and CRH-Cre each have unique patterns of expression restricted to thalamocortical neurons within and across the sensory relay nuclei of the dorsal thalamus. Cre expression is present by the time of natural birth in all three lines, underscoring their utility for developmental studies. To demonstrate the utility of these Cre drivers for studying sensory thalamocortical circuitry, we targeted expression of channelrhodopsin-2 to thalamus from the CAG-COP4*H134R/EYFP (Ai32) allele with either HDC-Cre or CRH-Cre. Optogenetic activation of thalamocortical afferents in primary visual cortex was sufficient to measure frequency-dependent depression. Thus, these Cre drivers provide selective Cre-dependent gene expression in thalamus suitable for both anatomical and functional studies. This article is protected by copyright. All rights reserved.

The thalamic reticular nucleus (TRN) is a shell-like structure comprised of GABAergic neurons that surrounds the dorsal thalamus. While playing a key role in modulating thalamocortical interactions, TRN inhibition of thalamic activity is often thought of as having an all-or-none impact. Although TRN neurons have a dynamic firing range, it remains unclear how variable rates of TRN activity gate thalamocortical transmission. To address this, we examined the ultrastructural features and functional synaptic properties of the feedback connections in the mouse thalamus between TRN and the dorsal lateral geniculate nucleus (dLGN), the principal relay of retinal signals to visual cortex. Using electron microscopy to identify TRN input to dLGN, we found that TRN terminals formed synapses with non-GABAergic postsynaptic profiles. Compared with other nonretinal terminals in dLGN, those from TRN were relatively large and tended to contact proximal regions of relay cell dendrites. To evoke TRN activity in dLGN, we adopted an optogenetic approach by expressing ChR2, or a variant (ChIEF) in TRN terminals. Both in vitro and in vivo recordings revealed that repetitive stimulation of TRN terminals led to a frequency-dependent inhibition of dLGN activity, with higher rates of stimulation resulting in increasing levels of membrane hyperpolarization and corresponding decreases in spike firing. This relationship suggests that alterations in TRN activity lead to graded changes in relay cell spike firing. NEW & NOTEWORTHY The thalamic reticular nucleus (TRN) modulates thalamocortical transmission through inhibition. In mouse, TRN terminals in the dorsal lateral geniculate nucleus (dLGN) form synapses with relay neurons but not interneurons. Stimulation of TRN terminals in dLGN leads to a frequency-dependent form of inhibition, with higher rates of stimulation leading to a greater suppression of spike firing. Thus, TRN inhibition appears more dynamic than previously recognized, having a graded rather than an all-or-none impact on thalamocortical transmission.

Cholinergic projections from the brainstem serve as important modulators of activity in visual thalamic nuclei such as the dorsal lateral geniculate nucleus (dLGN). While these projections have been studied in several mammals, a comprehensive examination of their organization in the mouse is lacking. We used the retrograde transport of viruses or cholera toxin subunit B (CTB) injected in the dLGN, immunocytochemical labeling with antibodies against choline acetyltransferase (ChAT), brain nitric oxide synthase (BNOS), and vesicular acetylcholine transporter (VAChT), ChAT-Cre mice crossed with a reporter line (Ai9), as well as brainstem virus injections in ChAT-Cre mice to examine the pattern of thalamic innervation from cholinergic neurons in the pedunculopontine tegmental nucleus (PPTg), laterodorsal tegmental nucleus (LDTg), and the parabigeminal nucleus (PBG). Retrograde tracing demonstrated that the dLGN receives input from the PPTg, LDTg, and PBG. Viral tracing in ChAT-Cre mice and retrograde tracing combined with immunocytochemistry revealed that many of these inputs originate from cholinergic neurons in the PBG and PPTg. Most notable was an extensive cholinergic projection from the PBG which innervated most of the contralateral dLGN, with an especially dense concentration in the dorsolateral shell, as well as a small region in the dorsomedial pole of the ipsilateral dLGN. The PPTg was found to provide a sparse somewhat diffuse innervation of the ipsilateral dLGN. Neurons in the PPTg co-expressed ChAT, BNOS, and VAChT, whereas PBG neurons expressed ChAT, but not BNOS or VAChT. These results highlight the presence of distinct cholinergic populations that innervate the mouse dLGN.

Retinofugal synapses serve as models for understanding how sensory signals from the periphery are relayed to the brain. Past studies have focused primarily on understanding the postsynaptic glutamatergic receptor subtypes involved in signal transmission, but the mechanisms underlying glutamate release at presynaptic retinal terminals remains largely unknown. Here we explored how different calcium (Ca2+) channel subtypes regulate glutamatergic excitatory synaptic transmission in two principal retinorecipient targets, the dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC) of the mouse. We used an in vitro slice preparation to record the synaptic responses of dLGN and SC neurons evoked by the electrical stimulation of optic tract (OT) fibers before and during the application of selective Ca2+ channel blockers. We found that synaptic responses to paired or repetitive OT stimulation were highly sensitive to extracellular levels of Ca2+ and to selective antagonists of voltage gated Ca2+ channels, indicating that these channels regulate the presynaptic release of glutamate at retinal synapses in both dLGN and SC. Bath application of selective Ca2+ channel blockers revealed that P/Q-type Ca2+ channels primarily operate to regulate glutamate release at retinal synapses in dLGN, while N-type Ca2+ channels dominate release in the SC.

El presente trabajo de investigación nos ha permitido conocer el nivel del Capital Intelectual de la empresa Estructuras Metálicas JRM SAC, en sus tres componentes Capital Humano, Capital Estructural y Capital Cliente que posee la empresa en base a una serie de indicadores propios del modelo de medición del capital intelectual navegador Skandia. De igual forma, en el estudio se utilizó información tomada del modelo de medición de Imagen Corporativa del Dr. Día Dumont (2015) basada en un cuestionario de preguntas orientadas a determinar la Imagen Comercial, Imagen Estratégica, Imagen Emocional e Imagen Social de la empresa. Asimismo, la investigación estuvo orientada a conocer la relación del Capital Intelectual con la Imagen Corporativa. En el estudio se utilizó como muestra el personal de la empresa agrupada en el nivel operativo, administrativo y comercial, así mismo se midió la percepción de los clientes con los que cuenta la compañía en un periodo determinado En conclusión, los resultados de la investigación muestran que el Capital Intelectual en la empresa Estructuras Metálicas JRM S.A.C es de nivel medio según lo establecido en el modelo navegador SKANDIA, y que existe una relación directa con la Imagen Corporativa según el coeficiente de Correlación de Spearman. De igual forma, en el estudio se identificaron componentes del Capital Intelectual que muestran un mayor desarrollo en comparación de sus otros componentes, lo cual representa una oportunidad de mejora para la compañía en implementar estrategias que permitan potenciar su nivel de Capital Intelectual en su componente Capital Humano, Capital Estructura y Capital Cliente. This research work has allowed us to know the level of Intellectual Capital of the company Estructuras Metálicas JRM SAC, in its three components Human Capital, Structural Capital and Client Capital that the company owns based on a series of indicators of the measurement model of the intellectual capital browser Skandia. In the same way, the study used information taken from the model of Corporate Image measurement of Dr. Día Dumont (2015) based on a questionnaire aimed at determining the Commercial Image, Strategic Image, Emotional Image and Social Image of the company. Likewise, the research was oriented to know the relationship of Intellectual Capital with the Corporate Image. In the study, the company personnel grouped at the operational, administrative and commercial level were used as a sample, as well as the perception of the clients that the company has in a given period. In conclusion, the results of the investigation show that the Intellectual Capital in the company Metallic Structures JRM SAC is of medium level as established in the SKANDIA navigator model, and that there is a direct relationship with the Corporate Image according to the Spearman Correlation coefficient. Similarly, the study identified components of Intellectual Capital that show greater development in comparison to its other components, which represents an opportunity for improvement for the company in implementing strategies that enhance its level of Intellectual Capital in its Capital component Human, Capital Structure and Client Capital. Tesis

Significance Local inhibition, mediated by thalamic interneurons, contributes to the processing of visual information and is essential for vision. However, the mechanisms underlying the development of these interneurons remains unresolved. In this study, we sought to identify mechanisms that contribute to the long-distance migration of these interneurons into the visual thalamus. Our data show that innervation of the visual thalamus by retinal ganglion cells, the output neurons of the retina, is necessary for normal interneuron migration. Surprisingly, axons from these retinal ganglion cells appear to signal through astrocytes to contribute to thalamic interneuron migration. Astrocyte-derived cues may be a general mechanism for guiding interneuron migration throughout the brain., Inhibitory interneurons comprise a fraction of the total neurons in the visual thalamus but are essential for sharpening receptive field properties and improving contrast-gain of retinogeniculate transmission. During early development, these interneurons undergo long-range migration from germinal zones, a process regulated by the innervation of the visual thalamus by retinal ganglion cells. Here, using transcriptomic approaches, we identified a motogenic cue, fibroblast growth factor 15 (FGF15), whose expression in the visual thalamus is regulated by retinal input. Targeted deletion of functional FGF15 in mice led to a reduction in thalamic GABAergic interneurons similar to that observed in the absence of retinal input. This loss may be attributed, at least in part, to misrouting of interneurons into nonvisual thalamic nuclei. Unexpectedly, expression analysis revealed that FGF15 is generated by thalamic astrocytes and not retino-recipient neurons. Thus, these data show that retinal inputs signal through astrocytes to direct the long-range recruitment of interneurons into the visual thalamus.

The dorsal lateral geniculate nucleus (dLGN) of the thalamus is the exclusive relay of retinal information en route to the visual cortex. Although much of our understanding about dLGN comes from studies done in higher mammals, such as the cat and primate, the mouse as a model organism has moved to the forefront as a tractable experimental platform to examine cell type-specific relations. This review highlights our current knowledge about the development, structure, and function of the mouse dLGN.

Receptive field properties of individual visual neurons are dictated by the precise patterns of synaptic connections they receive, including the arrangement of inputs in visual space and features such as polarity (On vs Off). The inputs from the retina to the lateral geniculate nucleus (LGN) in the mouse undergo significant refinement during development. However, it is unknown how this refinement corresponds to the establishment of functional visual response properties. Here we conductedin vivoandin vitrorecordings in the mouse LGN, beginning just after natural eye opening, to determine how receptive fields develop as excitatory and feedforward inhibitory retinal afferents refine. Experiments used both male and female subjects. Forin vivoassessment of receptive fields, we performed multisite extracellular recordings in awake mice. Spatial receptive fields at eye-opening were >2 times larger than in adulthood, and decreased in size over the subsequent week. This topographic refinement was accompanied by other spatial changes, such as a decrease in spot size preference and an increase in surround suppression. Notably, the degree of specificity in terms of On/Off and sustained/transient responses appeared to be established already at eye opening and did not change. We performedin vitrorecordings of the synaptic responses evoked by optic tract stimulation across the same time period. These recordings revealed a pairing of decreased excitatory and increased feedforward inhibitory convergence, providing a potential mechanism to explain the spatial receptive field refinement.SIGNIFICANCE STATEMENTThe development of precise patterns of retinogeniculate connectivity has been a powerful model system for understanding the mechanisms underlying the activity-dependent refinement of sensory systems. Here we link the maturation of spatial receptive field properties in the lateral geniculate nucleus (LGN) to the remodeling of retinal and inhibitory feedforward convergence onto LGN neurons. These findings should thus provide a starting point for testing the cell type-specific plasticity mechanisms that lead to refinement of different excitatory and inhibitory inputs, and for determining the effect of these mechanisms on the establishment of mature receptive fields in the LGN.

The dorsal lateral geniculate nucleus (dLGN) of the mouse is a model system to study the development of thalamic circuitry. Most studies focus on relay neurons of dLGN, yet little is known about the development of the other principal cell type, intrinsic interneurons. Here we examined whether the structure and function of interneurons relies on retinal signaling. We took a loss-of-function approach and crossed GAD67-GFP mice, which express GFP in dLGN interneurons, withmath5nulls (math5−/−), mutants that lack retinal ganglion cells and retinofugal projections.In vitrorecordings and 3-D reconstructions of biocytin-filled interneurons at different postnatal ages showed their development is a multistaged process involving migration, arbor remodeling, and synapse formation. Arbor remodeling begins during the second postnatal week, after migration to and dispersion within dLGN is complete. This phase includes a period of exuberant branching where arbors grow in number, complexity, and field size. Such growth is followed by branch pruning and stabilization, as interneurons adopt a bipolar architecture. The absence of retinal signaling disrupts this process. The math5−/−interneurons fail to branch and prune, and instead maintain a simple, sparse architecture. To test how such defects influence connectivity with dLGN relay neurons, we used DHPG [(RS)-3,5-dihydroxyphenylglycine], the mGluR1,5agonist that targets F2 terminals. This led to substantial increases in IPSC activity among WT relay neurons but had little impact in math5−/−mice. Together, these data suggest that retinal signaling is needed to support the arbor elaboration and synaptic connectivity of dLGN interneurons.SIGNIFICANCE STATEMENTPresently, our understanding about the development of the dorsal lateral geniculate nucleus is limited to circuits involving excitatory thalamocortical relay neurons. Here we show that the other principal cell type, intrinsic interneurons, has a multistaged developmental plan that relies on retinal innervation. These findings indicate that signaling from the periphery guides the maturation of interneurons and the establishment of inhibitory thalamic circuits.

El objetivo de la presente investigación fue demostrar que mediante el desarrollo de las competencias laborales del personal operativo en una empresa del Sector Metal mecánico permite contribuir con la implementación de un Sistema de Gestión de Calidad ISO 9001:2015. Las competencias laborales es una combinación de conocimientos, actitudes y habilidades. Para probar las hipótesis, se ha desarrollado una investigación no experimental, en la empresa Estanterías Metálicas JRM S.A.C, ubicada en el distrito de San Juan de Lurigancho, Lima, Perú. Se trabajó con los supervisores de producción y el personal operativo de las diversas áreas de productiva de la organización para la recopilación de información mediante el instrumento diseñado para medir las competencias laborales en relación a la gestión de calidad ISO 9001:2015.

Retinofugal synapses serve as models for understanding how sensory signals from the periphery are relayed to the brain. Past studies have focused primarily on understanding the postsynaptic glutamatergic receptor subtypes involved in signal transmission, but the mechanisms underlying glutamate release at presynaptic retinal terminals remains largely unknown. Here we explored how different calcium (Ca2+) channel subtypes regulate glutamatergic excitatory synaptic transmission in two principal retinorecipient targets, the dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC) of the mouse. We used anin vitroslice preparation to record the synaptic responses of dLGN and SC neurons evoked by the electrical stimulation of optic tract (OT) fibers before and during the application of selective Ca2+channel blockers. We found that synaptic responses to paired or repetitive OT stimulation were highly sensitive to extracellular levels of Ca2+and to selective antagonists of voltage gated Ca2+channels, indicating that these channels regulate the presynaptic release of glutamate at retinal synapses in both dLGN and SC. Bath application of selective Ca2+channel blockers revealed that P/Q-type Ca2+channels primarily operate to regulate glutamate release at retinal synapses in dLGN, while N-type Ca2+channels dominate release in the SC.

Despite the widespread adoption of uniportal video-assisted thoracoscopic surgery (UniVATS) for lung cancer, some procedures are still rarely performed with this approach. A minimally invasive approach is seldom selected to perform a pneumonectomy for a number of different reasons, usually involving the experience of the surgeon and the specific characteristics of cases requiring pneumonectomy as a treatment. Some surgeons believe that because of the complexity of such cases involving large tumors and usually some sort of hilum compromise, a minimally invasive technique cannot be safely performed. Safety involved in performing this procedure is more related to the surgeon experience in the approach than to the procedure itself, and it mostly depends on prior exposure to complex uniportal cases. In a time when several groups around the world are performing bronchovascular reconstructions, carinal resections by UniVATS the question should not be if is possible to perform UniVATS pneumonectomy, but what are the factors and considerations the surgeon must take into account in order to perform these cases. This review aims to provide an update on current status of uniportal VATS pneumonectomy and to provide guidance for surgeons who face this sort of cases.

The thalamic reticular nucleus (TRN), a shell-like structure comprised of GABAergic neurons, gates signal transmission between thalamus and cortex. While TRN is innervated by axon collaterals of thalamocortical and corticothalamic neurons, other ascending projections modulate activity during different behavioral states such as attention, arousal, and sleep-wake cycles. One of the largest arise from cholinergic neurons of the basal forebrain and brainstem. Despite its integral role, little is known about how or when cholinergic innervation and synapse formation occurs. We utilized genetically modified mice, which selectively express fluorescent protein and/or channelrhodopsin-2 in cholinergic neurons, to visualize and stimulate cholinergic afferents in the developing TRN. Cholinergic innervation of TRN follows a ventral-to-dorsal progression, with non-visual sensory sectors receiving input during week 1, and the visual sector during week 2. By week 3, the density of cholinergic fibers increases throughout TRN and forms a reticular profile. Functional patterns of connectivity between cholinergic fibers and TRN neurons progress in a similar manner, with weak excitatory nicotinic responses appearing in non-visual sectors near the end of week 1. By week 2, excitatory responses become more prevalent and arise in the visual sector. Between weeks 3–4, inhibitory muscarinic responses emerge, and responses become biphasic, exhibiting a fast excitatory, and a long-lasting inhibitory component. Overall, the development of cholinergic projections in TRN follows a similar plan as the rest of sensory thalamus, with innervation of non-visual structures preceding visual ones, and well after the establishment of circuits conveying sensory information from the periphery to the cortex.

The uniportal approach for major pulmonary resections began in 2010, with the first case being reported by D Gonzalez-Rivas and colleagues in La Coruna, Spain. Since then, in different countries, thoracic surgeons had been performing hundreds of cases, with more advanced and complex procedures. Nowadays, there are reports of uniportal tracheal resection and reconstruction, carinal resection, bronchoplastic procedures, lobectomies with en bloc chest wall excision, and vascular reconstruction with optimal outcomes. The development of technologies and the potential benefits of a direct view, anatomic instrumentation, better cosmesis, and, potentially, less postoperative pain have led uniportal video-assisted thoracic surgery to grow exponentially worldwide.

The link between neural activity and the refinement of projections from retina to the dorsal lateral geniculate nucleus (dLGN) of thalamus is based largely on studies that disrupt presynaptic retinogeniculate activity. Postsynaptic mechanisms responsible for implementing the activity-dependent remodeling in dLGN remain unknown. We tested whether L-type Ca2+channel activity in the form of synaptically evoked plateau potentials in dLGN cells is needed for remodeling by using a mutant mouse that lacks the ancillary β3subunit and, as a consequence, has highly reduced L-type channel expression and attenuated L-type Ca2+currents. In the dLGNs of β3-null mice, glutamatergic postsynaptic activity evoked by optic tract stimulation was normal, but plateau potentials were rarely observed. The few plateaus that were evoked required high rates of retinal stimulation, but were still greatly attenuated compared with those recorded in age-matched wild-type mice. While β3-null mice exhibit normal stage II and III retinal waves, their retinogeniculate projections fail to segregate properly and dLGN cells show a high degree of retinal convergence even at late postnatal ages. These structural and functional defects were also accompanied by a reduction in CREB phosphorylation, a signaling event that has been shown to be essential for retinogeniculate axon segregation. Thus, postsynaptic L-type Ca2+activity plays an important role in mediating the refinement of the retinogeniculate pathway.

Background The dorsal lateral geniculate nucleus (dLGN) of the mouse has become a model system for understanding thalamic circuit assembly. While the development of retinal projections to dLGN has been a topic of extensive inquiry, how and when nonretinal projections innervate this nucleus remains largely unexplored. In this study, we examined the development of a major nonretinal projection to dLGN, the ascending input arising from cholinergic neurons of the brainstem. To visualize these projections, we used a transgenic mouse line that expresses red fluorescent protein exclusively in cholinergic neurons. To assess whether retinal input regulates the timing and pattern of cholinergic innervation of dLGN, we utilized the math5-null (math5 −/−) mouse, which lacks retinofugal projections due to a failure of retinal ganglion cell differentiation. Results Cholinergic brainstem innervation of dLGN began at the end of the first postnatal week, increased steadily with age, and reached an adult-like pattern by the end of the first postnatal month. The absence of retinal input led to a disruption in the trajectory, rate, and pattern of cholinergic innervation of dLGN. Anatomical tracing experiments reveal these disruptions were linked to cholinergic projections from parabigeminal nucleus, which normally traverse and reach dLGN through the optic tract. Conclusions The late postnatal arrival of cholinergic projections to dLGN and their regulation by retinal signaling provides additional support for the existence of a conserved developmental plan whereby retinal input regulates the timing and sequencing of nonretinal projections to dLGN.

The dorsal lateral geniculate nucleus (dLGN) of the thalamus is the principal conduit for visual information from retina to visual cortex. Viewed initially as a simple relay, recent studies in the mouse reveal far greater complexity in the way input from the retina is combined, transmitted, and processed in dLGN. Here we consider the structural and functional organization of the mouse retinogeniculate pathway by examining the patterns of retinal projections to dLGN and how they converge onto thalamocortical neurons to shape the flow of visual information to visual cortex.

The pulvinar nucleus is a large thalamic structure involved in the integration of visual and motor signals. The pulvinar forms extensive connections with striate and extrastriate cortical areas, but the impact of these connections on cortical circuits has not previously been directly tested. Using a variety of anatomical, optogenetic, andin vitrophysiological techniques in male and female mice, we show that pulvinocortical terminals are densely distributed in the extrastriate cortex where they form synaptic connections with spines and small-diameter dendrites. Optogenetic activation of these synapsesin vitroevoked large excitatory postsynaptic responses in the majority of pyramidal cells, spiny stellate cells, and interneurons within the extrastriate cortex. However, specificity in pulvinar targeting was revealed when recordings were targeted to projection neuron subtypes. The neurons most responsive to pulvinar input were those that project to the striatum and amygdala (76% responsive) or V1 (55%), whereas neurons that project to the superior colliculus were rarely responsive (6%). Because the pulvinar also projects directly to the striatum and amygdala, these results establish the pulvinar nucleus as a hub linking the visual cortex with subcortical regions involved in the initiation and control of movement. We suggest that these circuits may be particularly important for coordinating body movements and visual perception.SIGNIFICANCE STATEMENTWe found that the pulvinar nucleus can strongly influence extrastriate cortical circuits and exerts a particularly strong impact on the activity of extrastriate neurons that project to the striatum and amygdala. Our results suggest that the conventional hierarchical view of visual cortical processing may not apply to the mouse visual cortex. Instead, our results establish the pulvinar nucleus as a hub linking the visual cortex with subcortical regions involved in the initiation and control of movement, and predict that the execution of visually guided movements relies on this network.

Las organizaciones que desean ser cada vez más competitivas requieren desarrollar las competencias del personal, optimizando su potencial para lograr altos niveles de competitividad y satisfacción. Los modelos tradicionales definen perfiles de puestos sin contemplar un análisis profundo sobre el desarrollo de competencias del personal. La investigación presenta dos variables: competencia laboral y gestión de calidad ISO 9001:2015 y está orientada a determinar la relación entre ambas, para luego determinar que competencias requieren ser desarrolladas mediante planes de acción. Para la obtención de información, procesamiento de datos y análisis de resultados se diseñó un cuestionario, validado por expertos, aplicable a la naturaleza de la empresa y sea entendible por el personal operativo durante la investigación. Asimismo, la investigación se llevó a cabo en una empresa peruana del sector metalmecánico, ubicado en el distritito de San Juan de Lurigancho. Se utilizó como muestra el personal operativo representado por cada una de las áreas de producción, se aplicaron una variedad de técnicas científicas de trabajo de campo, principalmente guías de observación, para demostrar la hipótesis planteada y posteriormente generar una propuesta a desarrollar. En suma, el resultado de la investigación muestra que el instrumento diseñado para medir las variables de estudio es aceptable con significancia moderada. En base a la investigación presentada, se identificó que hay áreas operativas que cuentan con personal con competencias más desarrolladas que otras en sus puestos de trabajo, y otras que requieren reforzamiento referente a los aspectos técnicos de la operación y requisitos significantes de un Sistema de Gestión de Calidad ISO. Finalmente, se muestran las conclusiones y recomendaciones de mejoras para contrarrestar los puntos débiles identificados y que contribuya a mejorar el desempeño de los procesos operativos en la organización.

Neural circuit formation demands precise timing of innervation by different classes of axons. However, the mechanisms underlying such activity remain largely unknown. In the dorsal lateral geniculate nucleus (dLGN), axons from the retina and visual cortex innervate thalamic relay neurons in a highly coordinated manner, with those from the cortex arriving well after those from retina. The differential timing of retino- and corticogeniculate innervation is not a coincidence but is orchestrated by retinal inputs. Here, we identified a chondroitin sulfate proteoglycan (CSPG) that regulates the timing of corticogeniculate innervation. Aggrecan, a repulsive CSPG, is enriched in neonatal dLGN and inhibits cortical axons from prematurely entering the dLGN. Postnatal loss of aggrecan from dLGN coincides with upregulation of aggrecanase expression in the dLGN and corticogeniculate innervation and, it is important to note, is regulated by retinal inputs. Taken together, these studies reveal a molecular mechanism through which one class of axons coordinates the temporal targeting of another class of axons. National Institutes of Health NIH: EY012716 NIH: EY021222

Purpose The prevalence of minimally invasive lung cancer surgery using video-assisted thoracic surgery (VATS) has increased dramatically over the past decade, yet recent studies have suggested that the lymph node evaluation during VATS lobectomy is inadequate. We hypothesized that the minimally invasive approach to lobectomy for stage I lung cancer resulted in a longitudinal outcome that was not inferior to thoracotomy. Patients and Methods Patients65 years of age who had undergone lobectomy for stage I lung cancer between 2002 and 2013 were analyzed within the Society of Thoracic Surgeons General Thoracic Surgery Database, which had been linked to Medicare data, as part of a retrospective-cohort, noninferiority study. Results A total of 10,597 patients with clinical stage I lung cancer who underwent lobectomy were evaluated (4,448 patients underwent thoracotomy, and 6,149 underwent VATS). VATS patients had a more favorable distribution of all health-related variables, including pulmonary function (59% of VATS patients had intact spirometry v 51% of thoracotomy patients; P.001). Cox proportional hazards models were performed over two eras to account for an evolving practice standard. The mortality risk associated with the VATS approach was not greater than thoracotomy in either the earlier era (2002 to 2008; hazard ratio, 0.97; 95% CI, 0.87 to 1.09; P = .62) or the more recent era (2009 to 2013; hazard ratio, 0.84; 95% CI, 0.75 to 0.93; P.001). Kaplan-Meier survival estimates of 2,901 propensity-matched VATS-thoracotomy pairs demonstrated that the 4-year survival associated with VATS (68.6%) was modestly superior to thoracotomy (64.8%; P = .003). The analyses detailed above were replicated in a separate cohort of pathologic stage I patients with similar findings. Conclusion The long-term efficacy of lobectomy for stage I lung cancer performed using the VATS approach by board-certified thoracic surgeons does not seem to be inferior to that of thoracotomy.

Neurons in layer VI of visual cortex represent one of the largest sources of nonretinal input to the dorsal lateral geniculate nucleus (dLGN) and play a major role in modulating the gain of thalamic signal transmission. However, little is known about how and when these descending projections arrive and make functional connections with dLGN cells. Here we used a transgenic mouse to visualize corticogeniculate projections to examine the timing of cortical innervation in dLGN. Corticogeniculate innervation occurred at postnatal ages and was delayed compared with the arrival of retinal afferents. Cortical fibers began to enter dLGN at postnatal day 3 (P3) to P4, a time when retinogeniculate innervation is complete. However, cortical projections did not fully innervate dLGN until eye opening (P12), well after the time when retinal inputs from the two eyes segregate to form nonoverlapping eye-specific domains. In vitro thalamic slice recordings revealed that newly arriving cortical axons form functional connections with dLGN cells. However, adult-like responses that exhibited paired pulse facilitation did not fully emerge until 2 weeks of age. Finally, surgical or genetic elimination of retinal input greatly accelerated the rate of corticogeniculate innervation, with axons invading between P2 and P3 and fully innervating dLGN by P8 to P10. However, recordings in genetically deafferented mice showed that corticogeniculate synapses continued to mature at the same rate as controls. These studies suggest that retinal and cortical innervation of dLGN is highly coordinated and that input from retina plays an important role in regulating the rate of corticogeniculate innervation.

Background Human immunodeficiency virus (HIV) associated neurocognitive disorders (HAND), including memory dysfunction, continue to be a major clinical manifestation of HIV type-1 infection. Viral proteins released by infected glia are thought to be the principal triggers of inflammation and bystander neuronal injury and death, thereby driving key symptomatology of HAND. Methods We used a glial fibrillary acidic protein-driven, doxycycline-inducible HIV type-1 transactivator of transcription (Tat) transgenic mouse model and examined structure-function relationships in hippocampal pyramidal cornu ammonis 1 (CA1) neurons using morphologic, electrophysiological (long-term potentiation [LTP]), and behavioral (Morris water maze, fear-conditioning) approaches. Results Tat induction caused a variety of different inclusions in astrocytes characteristic of lysosomes, autophagic vacuoles, and lamellar bodies, which were typically present within distal cytoplasmic processes. In pyramidal CA1 neurons, Tat induction reduced the number of apical dendritic spines, while disrupting the distribution of synaptic proteins (synaptotagmin 2 and gephyrin) associated with inhibitory transmission but with minimal dendritic pathology and no evidence of pyramidal neuron death. Electrophysiological assessment of excitatory postsynaptic field potential at Schaffer collateral/commissural fiber-CA1 synapses showed near total suppression of LTP in mice expressing Tat. The loss in LTP coincided with disruptions in learning and memory. Conclusions Tat expression in the brain results in profound functional changes in synaptic physiology and in behavior that are accompanied by only modest structural changes and minimal pathology. Tat likely contributes to HAND by causing molecular changes that disrupt synaptic organization, with inhibitory presynaptic terminals containing synaptotagmin 2 appearing especially vulnerable.

Video-assisted thoracoscopic surgery (VATS) has experience an exponential growth in lung anatomic resections. Since its beginnings in early 90s with the conventional multiport VATS to the more recent uniportal approach, a continuous search for a less invasive procedure has fueled the development of minimally invasive thoracic surgery. In this sense, subxiphoid uniportal VATS has surge as a uniportal option that avoids damage to the intercostal nerve created in a transthoracic approach. In order for this technique to become as an acceptable choice for lung cancer, oncologic principles must be respected, including a feasible and safe mediastinal lymphadenectomy. Although technically more difficult than other VATS approaches, a complete lymphadenectomy is possible in the hands of expert VATS surgeons through a subxiphoid approach.

The uniportal approach for major pulmonary resections began in 2010 with the first case being performed by Gonzalez-Rivas and colleagues in La Coruna. Since then a number of teams around the world had being performing hundreds of cases, applying it to more advance and complex cases recently. The technique has been reported to be feasible and reliable with similar results to that obtained in early stage lung cancer lobectomies. The case presented in this article is an example of an extreme condition: very obese patient, strong adhesions, fused lower lobe to the diaphragm and enlarged inflammatory adenopathies that made the procedure very technically challenging. In addition, the surgery was performed during a live surgery event and it was broadcasted to an auditorium. However, the case was successfully completed through a uniportal VATS approach with no complications.