Visual subcircuit-specific dysfunction and input-specific mispatterning in the superior colliculus of fragile X mice

Abstract Background Sensory processing deficits are frequently co-morbid with neurodevelopmental disorders. For example, patients with fragile X syndrome (FXS), caused by a silencing of the FMR1 gene, exhibit impairments in visual function specific to the dorsal system, which processes motion information. However, the developmental and circuit mechanisms underlying this deficit remain unclear. Recently, the superior colliculus (SC), a midbrain structure regulating head and eye movements, has emerged as a model for dissecting visual circuit development and function. Previous studies have demonstrated a critical role for activity-dependent processes in the development of visual circuitry in the SC. Based on the known role of the FMR1 gene product in activity-dependent synaptic plasticity, we explored the function and organization of visual circuits in the SC of a mouse model of FXS (Fmr1−/y). Methods We utilized in vivo extracellular electrophysiology in combination with computer-controlled visual stimuli to determine the receptive field properties of visual neurons in the SC of control and Fmr1−/y mice. In addition, we utilized anatomical tracing methods to assess the organization of visual inputs to the SC and along the retinogeniculocortical pathway. Results Receptive fields of visual neurons in the SC of Fmr1−/y mice were significantly larger than those found in control animals, though their shape and structure were unaffected. Further, selectivity for direction of movement was decreased, while selectivity to axis of movement was unchanged. Interestingly, axis-selective (AS) neurons exhibited a specific hyperexcitability in comparison to AS neurons in control SC and to direction-selective (DS) neurons in both control and Fmr1−/y SC. Anatomical tracings revealed that retinocollicular, retinogeniculate, and geniculocortical projections were normally organized in the absence of Fmr1. However, projections from primary visual cortex (V1) to the SC were poorly refined. Conclusions Fmr1 is required for the proper development of visual circuit organization and function in the SC. We find that visual dysfunction is heterogeneously manifested in a subcircuit-specific manner in Fmr1−/y mice, consistent with previous studies in human FXS patients. Further, we show a specific alteration of inputs to the SC from V1, but not the retina. Together, these data suggest that Fmr1 may function in distinct ways during the development of different visual subcircuits.https://deepblue.lib.umich.edu/bitstream/2027.42/144523/1/11689_2018_Article_9241.pd

Dendritic and axonal targeting patterns of a genetically-specified class of retinal ganglion cells that participate in image-forming circuits.

BackgroundThere are numerous functional types of retinal ganglion cells (RGCs), each participating in circuits that encode a specific aspect of the visual scene. This functional specificity is derived from distinct RGC morphologies and selective synapse formation with other retinal cell types; yet, how these properties are established during development remains unclear. Islet2 (Isl2) is a LIM-homeodomain transcription factor expressed in the developing retina, including approximately 40% of all RGCs, and has previously been implicated in the subtype specification of spinal motor neurons. Based on this, we hypothesized that Isl2+ RGCs represent a related subset that share a common function.ResultsWe morphologically and molecularly characterized Isl2+ RGCs using a transgenic mouse line that expresses GFP in the cell bodies, dendrites and axons of Isl2+ cells (Isl2-GFP). Isl2-GFP RGCs have distinct morphologies and dendritic stratification patterns within the inner plexiform layer and project to selective visual nuclei. Targeted filling of individual cells reveals that the majority of Isl2-GFP RGCs have dendrites that are monostratified in layer S3 of the IPL, suggesting they are not ON-OFF direction-selective ganglion cells. Molecular analysis shows that most alpha-RGCs, indicated by expression of SMI-32, are also Isl2-GFP RGCs. Isl2-GFP RGCs project to most retino-recipient nuclei during early development, but specifically innervate the dorsal lateral geniculate nucleus and superior colliculus (SC) at eye opening. Finally, we show that the segregation of Isl2+ and Isl2- RGC axons in the SC leads to the segregation of functional RGC types.ConclusionsTaken together, these data suggest that Isl2+ RGCs comprise a distinct class and support a role for Isl2 as an important component of a transcription factor code specifying functional visual circuits. Furthermore, this study describes a novel genetically-labeled mouse line that will be a valuable resource in future investigations of the molecular mechanisms of visual circuit formation

Work-worlds colliding: Self-reflexivity, power and emotion in organizational ethnography

While organizational ethnographers have embraced the concept of self-reflexivity, problems remain. In this article we argue that the prevalent assumption that self-reflexivity is the sole responsibility of the individual researcher limits its scope for understanding organizations. To address this, we propose an innovative method of collective reflection that is inspired by ideas from cultural and feminist anthropology. The value of this method is illustrated through an analysis of two ethnographic case studies, involving a ‘pair interview’ method. This collective approach surfaced self-reflexive accounts, in which aspects of the research encounter that still tend to be downplayed within organizational ethnographies, including emotion, intersubjectivity and the operation of power dynamics, were allowed to emerge. The approach also facilitated a second contribution through the conceptualization of organizational ethnography as a unique endeavour that represents a collision between one ‘world of work’: the university, with a second: the researched organization. We find that this ‘collision’ exacerbates the emotionality of ethnographic research, highlighting the refusal of ‘researched’ organizations to be domesticated by the specific norms of academia. Our article concludes by drawing out implications for the practice of self-reflexivity within organizational ethnography

CRITICAL FIELD FOR SUPERCONDUCTIVITY AND LOW-TEMPERATURE NORMAL-STATE HEAT CAPACITY OF TUNGSTEN

We have measured the critical magnetic field for superconductivity In tungsten from 5.5 to 15 mK using a {gamma}-ray anisotropy thermometer, and we have measured the heat capacity between 0.35 and 25 K. Analysis of the data gives H{sub 0} = 1.237 Oe for the 0 K critical field, T{sub c} = 16.0 mK for the critical temperature, {gamma} = 1.008 mJ/mole K{sup 2} for the coefficient of the electronic heat capacity, and {Theta}{sub 0} = 383 K for the 0 K Debye temperature. The measured values of the critical field H{sub c} are consistently higher than those reported by Black, Johnson and Wheatley (BJW) on the CMN temperature scale, but the temperature dependence is similar. This discrepancy and the temperature dependence of H{sub c} suggest that both sets of H{sub c} data are affected by magnetic impurities. Use of the calorimetric {gamma} value permits an improved test of the CMN temperature scale with the very low temperature H{sub c} data obtained by BJW

Comparative Proteomic Analyses of the Parietal Lobe from Rhesus Monkeys Fed a High-Fat/Sugar Diet With and Without Resveratrol Supplementation, Relative to a Healthy Diet: Insights Into the Roles of Unhealthy Diets and Resveratrol on Function

A diet consisting of a high intake of saturated fat and refined sugars is characteristic of a Western-diet and has been shown to have a substantial negative effect on human health. Expression proteomics were used to investigate changes to the parietal lobe proteome of rhesus monkeys consuming either a high fat and sugar (HFS) diet, a HFS diet supplemented with resveratrol (HFS+RSV), or a healthy control diet for 2 years. Here we discuss the modifications in the levels of 12 specific proteins involved in various cellular systems including metabolism, neurotransmission, structural integrity, and general cellular signaling following a nutritional intervention. Our results contribute to a better understanding of the mechanisms by which resveratrol functions through the up- or down-regulation of proteins in different cellular sub-systems to affect the overall health of the brain

The role of charge in the toxicity of polymer-coated cerium oxide nanomaterials to Caenorhabditis elegans

This study examined the impact of surface functionalization and charge on ceria nanomaterial toxicity to Caenorhabditis elegans. The examined endpoints included mortality, reproduction, protein expression, and protein oxidation profiles. Caenorhabditis elegans were exposed to identical 2–5 nm ceria nanomaterial cores which were coated with cationic (diethylaminoethyl dextran; DEAE), anionic (carboxymethyl dextran; CM), and non-ionic (dextran; DEX) polymers. Mortality and reproductive toxicity of DEAE-CeO2 was approximately two orders of magnitude higher than for CM-CeO2 or DEX-CeO2. Two-dimensional gel electrophoresis with orbitrap mass spectrometry identification revealed changes in the expression profiles of several mitochondrial-related proteins and proteins that are expressed in the C. elegans intestine. However, each type of CeO2 material exhibited a distinct protein expression profile. Increases in protein carbonyls and protein-bound 3-nitrotyrosine were also observed for some proteins, indicating oxidative and nitrosative damage. Taken together the results indicate that the magnitude of toxicity and toxicity pathways vary greatly due to surface functionalization of CeO2 nanomaterials

Microscopic theory of quadrupolar ordering in TmTe

We have calculated the crystal electric field of TmTe (T>T_Q) and have obtained that the ground state of a Tm 4f hole is the $\Gamma_7$ doublet in agreement with Mossbauer experiments. We study the quadrupole interactions arising from quantum transitions of 4f holes of Tm. An effective attraction is found at the L point of the Brillouin zone, $\vec{q}_L$. Assuming that the quadrupolar condensation involves a single arm of $\vec{q}_L$ we show that there are two variants for quadrupole ordering which are described by the space groups C2/c and C2/m. The Landau free energy is derived in mean-field theory. The phase transition is of second order. The corresponding quadrupole order parameters are combinations of $T_{2g}$ and $E_g$ components. The obtained domain structure is in agreement with observations from neutron diffraction studies for TmTe. Calculated lattice distortions are found to be different for the two variants of quadrupole ordering. We suggest to measure lattice displacements in order to discriminate between those two structures.Comment: 10 pages, 2 figures, 5 tables; accepted by PR