ResearchPad - nerve-fibers https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Interplay between axonal Wnt5-Vang and dendritic Wnt5-Drl/Ryk signaling controls glomerular patterning in the <i>Drosophila</i> antennal lobe]]> https://www.researchpad.co/article/elastic_article_14504 During brain development, the processes of nerve cells, axons and dendrites, grow over long distances to find and connect with each other to form synapses in precise locations. Understanding the mechanisms that control the growth of these neurites is important for understanding normal brain functions like neuronal plasticity and neural diseases like autism. Although much progress has been made by studying the development of axons and dendrites separately, the mechanisms that guide neuronal processes to their final locations are still incompletely understood. In particular, careful observation of converging pre- and postsynaptic processes suggests that their targeting may be coordinated. Whether the final targeting of axons and dendrites are functionally linked and what molecular mechanisms may be involved are unknown. In this paper we show that, in the developing Drosophila olfactory circuit, coalescing axons and dendrites respond to the extracellular Wnt5 signal in a codependent manner. We demonstrate that the converging axons and dendrites contribute different signaling components to the Wnt5 pathway, the Vang Gogh and Derailed transmembrane receptors respectively, which allow Wnt5 to coordinately guide the targeting of the neurites. Our work thus reveals a novel mechanism of neural circuit patterning and the molecular mechanism that controls it.

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<![CDATA[Low-rate firing limit for neurons with axon, soma and dendrites driven by spatially distributed stochastic synapses]]> https://www.researchpad.co/article/elastic_article_13830 Neurons are extended cells with multiple branching dendrites, a cell body and an axon. In an active neuronal network, neurons receive vast numbers of incoming synaptic pulses throughout their dendrites and cell body that each exhibit significant variability in amplitude and arrival time. The resulting synaptic input causes voltage fluctuations throughout their structure that evolve in space and time. The dynamics of how these signals are integrated and how they ultimately trigger outgoing spikes have been modelled extensively since the late 1960s. However, until relatively recently the majority of the mathematical formulae describing how fluctuating synaptic drive triggers action potentials have been applicable only for small neurons with the dendritic and axonal structure ignored. This has been largely due to the mathematical complexity of including the effects of spatially distributed synaptic input. Here we show that in a physiologically relevant, low-firing-rate regime, an approximate level-crossing approach can be used to provide an estimate for the neuronal firing rate even when the dendrites and axons are included. We illustrate this approach using basic neuronal morphologies that capture the fundamentals of neuronal structure. Though the models are simple, these preliminary results show that it is possible to obtain useful formulae that capture the effects of spatially distributed synaptic drive. The generality of these results suggests they will provide a mathematical framework for future studies that might require the structure of neurons to be taken into account, such as the effect of electrical fields or multiple synaptic input streams that target distinct spatial domains of cortical pyramidal cells.

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<![CDATA[Noninvasive vagus nerve stimulation alters neural response and physiological autonomic tone to noxious thermal challenge]]> https://www.researchpad.co/article/5c6dca21d5eed0c48452a80d

The mechanisms by which noninvasive vagal nerve stimulation (nVNS) affect central and peripheral neural circuits that subserve pain and autonomic physiology are not clear, and thus remain an area of intense investigation. Effects of nVNS vs sham stimulation on subject responses to five noxious thermal stimuli (applied to left lower extremity), were measured in 30 healthy subjects (n = 15 sham and n = 15 nVNS), with fMRI and physiological galvanic skin response (GSR). With repeated noxious thermal stimuli a group × time analysis showed a significantly (p < .001) decreased response with nVNS in bilateral primary and secondary somatosensory cortices (SI and SII), left dorsoposterior insular cortex, bilateral paracentral lobule, bilateral medial dorsal thalamus, right anterior cingulate cortex, and right orbitofrontal cortex. A group × time × GSR analysis showed a significantly decreased response in the nVNS group (p < .0005) bilaterally in SI, lower and mid medullary brainstem, and inferior occipital cortex. Finally, nVNS treatment showed decreased activity in pronociceptive brainstem nuclei (e.g. the reticular nucleus and rostral ventromedial medulla) and key autonomic integration nuclei (e.g. the rostroventrolateral medulla, nucleus ambiguous, and dorsal motor nucleus of the vagus nerve). In aggregate, noninvasive vagal nerve stimulation reduced the physiological response to noxious thermal stimuli and impacted neural circuits important for pain processing and autonomic output.

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<![CDATA[Association of small fiber neuropathy and post treatment Lyme disease syndrome]]> https://www.researchpad.co/article/5c6c75a6d5eed0c4843cff72

Objectives

To examine whether post-treatment Lyme disease syndrome (PTLDS) defined by fatigue, cognitive complaints and widespread pain following the treatment of Lyme disease is associated with small fiber neuropathy (SFN) manifesting as autonomic and sensory dysfunction.

Methods

This single center, retrospective study evaluated subjects with PTLDS. Skin biopsies for assessment of epidermal nerve fiber density (ENFD), sweat gland nerve fiber density (SGNFD) and functional autonomic testing (deep breathing, Valsalva maneuver and tilt test) were performed to assess SFN, severity of dysautonomia and cerebral blood flow abnormalities. Heart rate, end tidal CO2, blood pressure, and cerebral blood flow velocity (CBFv) from middle cerebral artery using transcranial Doppler were monitored.

Results

10 participants, 5/5 women/men, age 51.3 ± 14.7 years, BMI 27.6 ± 7.3 were analyzed. All participants were positive for Lyme infection by CDC criteria. At least one skin biopsy was abnormal in all ten participants. Abnormal ENFD was found in 9 participants, abnormal SGNFD in 5 participants, and both abnormal ENFD and SGNFD were detected in 4 participants. Parasympathetic failure was found in 7 participants and mild or moderate sympathetic adrenergic failure in all participants. Abnormal total CBFv score was found in all ten participants. Low orthostatic CBFv was found in 7 participants, three additional participants had abnormally reduced supine CBFv.

Conclusions

SFN appears to be associated with PTLDS and may be responsible for certain sensory symptoms. In addition, dysautonomia related to SFN and abnormal CBFv also seem to be linked to PTLDS. Reduced orthostatic CBFv can be associated with cerebral hypoperfusion and may lead to cognitive dysfunction. Autonomic failure detected in PTLDS is mild to moderate. SFN evaluation may be useful in PTLDS.

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<![CDATA[Regenerative capacity in the lamprey spinal cord is not altered after a repeated transection]]> https://www.researchpad.co/article/5c5b52bbd5eed0c4842bcf38

The resilience of regeneration in vertebrates is not very well understood. Yet understanding if tissues can regenerate after repeated insults, and identifying limitations, is important for elucidating the underlying mechanisms of tissue plasticity. This is particularly challenging in tissues, such as the nervous system, which possess a large number of terminally differentiated cells and often exhibit limited regeneration in the first place. However, unlike mammals, which exhibit very limited regeneration of spinal cord tissues, many non-mammalian vertebrates, including lampreys, bony fishes, amphibians, and reptiles, regenerate their spinal cords and functionally recover even after a complete spinal cord transection. It is well established that lampreys undergo full functional recovery of swimming behaviors after a single spinal cord transection, which is accompanied by tissue repair at the lesion site, as well as axon and synapse regeneration. Here we begin to explore the resilience of spinal cord regeneration in lampreys after a second spinal transection (re-transection). We report that by all functional and anatomical measures tested, lampreys regenerate after spinal re-transection just as robustly as after single transections. Recovery of swimming, synapse and cytoskeletal distributions, axon regeneration, and neuronal survival were nearly identical after spinal transection or re-transection. Only minor differences in tissue repair at the lesion site were observed in re-transected spinal cords. Thus, regenerative potential in the lamprey spinal cord is largely unaffected by spinal re-transection, indicating a greater persistent regenerative potential than exists in some other highly regenerative models. These findings establish a new path for uncovering pro-regenerative targets that could be deployed in non-regenerative conditions.

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<![CDATA[Exploring the effects of electrospun fiber surface nanotopography on neurite outgrowth and branching in neuron cultures]]> https://www.researchpad.co/article/5c61e8c9d5eed0c48496f18d

Three aligned, electrospun fiber scaffolds with unique surface features were created from poly-L-lactic acid (PLLA). Fibers without surface nanotopography (smooth fibers), fibers with surface divots (shallow pits), and fibers with surface pits (deeper pits) were fabricated, and fiber alignment, diameter, and density were characterized using scanning electron microscopy (SEM). Whole dorsal root ganglia (DRG) were isolated from rats and placed onto uncoated fibers or fibers coated with laminin. On uncoated fibers, neurite outgrowth was restricted by fibers displaying divoted or pitted nanotopography when compared to neurite outgrowth on smooth fibers. However, neurites extending from whole DRG cultured on laminin-coated fibers were not restricted by divoted or pitted surface nanotopography. Thus, neurites extending on laminin-coated fibers were able to extend long neurites even in the presence of surface divots or pits. To further explore this result, individual neurons isolated from dissociated DRG were seeded onto laminin-coated smooth, pitted, or divoted fibers. Interestingly, neurons on pitted or divoted fibers exhibited a 1.5-fold increase in total neurite length, and a 2.3 or 2.7-fold increase in neurite branching compared to neurons on smooth fibers, respectively. Based on these findings, we conclude that fiber roughness in the form of pits or divots can promote extension and branching of long neurites along aligned electrospun fibers in the presence of an extracellular matrix protein coating. Thus, aligned, electrospun fibers can be crafted to not only direct the extension of axons but to induce unique branching morphologies.

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<![CDATA[Diapause induces functional axonal regeneration after necrotic insult in C. elegans]]> https://www.researchpad.co/article/5c46652ed5eed0c484517d84

Many neurons are unable to regenerate after damage. The ability to regenerate after an insult depends on life stage, neuronal subtype, intrinsic and extrinsic factors. C. elegans is a powerful model to test the genetic and environmental factors that affect axonal regeneration after damage, since its axons can regenerate after neuronal insult. Here we demonstrate that diapause promotes the complete morphological regeneration of truncated touch receptor neuron (TRN) axons expressing a neurotoxic MEC-4(d) DEG/ENaC channel. Truncated axons of different lengths were repaired during diapause and we observed potent axonal regrowth from somas alone. Complete morphological regeneration depends on DLK-1 but neuronal sprouting and outgrowth is DLK-1 independent. We show that TRN regeneration is fully functional since animals regain their ability to respond to mechanical stimulation. Thus, diapause induced regeneration provides a simple model of complete axonal regeneration which will greatly facilitate the study of environmental and genetic factors affecting the rate at which neurons die.

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<![CDATA[A transient helix in the disordered region of dynein light intermediate chain links the motor to structurally diverse adaptors for cargo transport]]> https://www.researchpad.co/article/5c3d00f2d5eed0c484036f67

All animal cells use the motor cytoplasmic dynein 1 (dynein) to transport diverse cargo toward microtubule minus ends and to organize and position microtubule arrays such as the mitotic spindle. Cargo-specific adaptors engage with dynein to recruit and activate the motor, but the molecular mechanisms remain incompletely understood. Here, we use structural and dynamic nuclear magnetic resonance (NMR) analysis to demonstrate that the C-terminal region of human dynein light intermediate chain 1 (LIC1) is intrinsically disordered and contains two short conserved segments with helical propensity. NMR titration experiments reveal that the first helical segment (helix 1) constitutes the main interaction site for the adaptors Spindly (SPDL1), bicaudal D homolog 2 (BICD2), and Hook homolog 3 (HOOK3). In vitro binding assays show that helix 1, but not helix 2, is essential in both LIC1 and LIC2 for binding to SPDL1, BICD2, HOOK3, RAB-interacting lysosomal protein (RILP), RAB11 family-interacting protein 3 (RAB11FIP3), ninein (NIN), and trafficking kinesin-binding protein 1 (TRAK1). Helix 1 is sufficient to bind RILP, whereas other adaptors require additional segments preceding helix 1 for efficient binding. Point mutations in the C-terminal helix 1 of Caenorhabditis elegans LIC, introduced by genome editing, severely affect development, locomotion, and life span of the animal and disrupt the distribution and transport kinetics of membrane cargo in axons of mechanosensory neurons, identical to what is observed when the entire LIC C-terminal region is deleted. Deletion of the C-terminal helix 2 delays dynein-dependent spindle positioning in the one-cell embryo but overall does not significantly perturb dynein function. We conclude that helix 1 in the intrinsically disordered region of LIC provides a conserved link between dynein and structurally diverse cargo adaptor families that is critical for dynein function in vivo.

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<![CDATA[Growth factors expression and ultrastructural morphology after application of low-level laser and natural latex protein on a sciatic nerve crush-type injury]]> https://www.researchpad.co/article/5c3fa5aad5eed0c484ca713c

The effects of low-level laser therapy (LLLT) and natural latex protein (F1, Hevea brasiliensis) were evaluated on crush-type injuries (15kg) to the sciatic nerve in the expressions of nerve growth factor (NGF) and vascular endothelium growth factor (VEGF) and ultrastructural morphology to associate with previous morphometric data using the same protocol of injury and treatment. Thirty-six male rats were allocated into six experimental groups (n = 6): 1-Control; 2-Exposed nerve; 3-Injured nerve; 4-LLLT (15J/cm2, 780nm, 30mW, Continuous Wave) treated injured nerve; 5-F1 (0,1mg) treated injured nerve; and 6-LLLT&F1 treated injured nerve. Four or eight weeks after, sciatic nerve samples were processed for analysis. NGF expression were higher (p<0.05) four weeks after in all injured groups in comparison to Control (Med:0.8; Q1:0; Q3:55.5%area). Among them, the Injured (Med:70.7; Q1:64.4; Q3:77.5%area) showed the highest expression, and F1 (Med:17.3; Q1:14.1; Q3:21.7%area) had the lowest. At week 8, NGF expressions decreased in the injured groups. VEGF was expressed in all groups; its higher expression was observed in the injured groups 4 weeks after (Injured. Med:29.5; F1. Med:17.7 and LLLT&F1. Med:19.4%area). At week 8, a general reduction of VEGF expression was noted, remaining higher in F1 (Med:35.1; Q1.30.6; Q3.39.6%area) and LLLT&F1 (Med:18.5; Q1:16; Q3:25%area). Ultrastructural morphology revealed improvements in the treated groups; 4 weeks after, the F1 group presented greater quantity and diameter of the nerve fibers uniformly distributed. Eight weeks after, the F1 and LLLT&F1 showed similar characteristics to the non-injured groups. In summary, these results and our previous studies indicated that F1 and LLLT may favorably influence the healing of nerve crush injury. Four weeks after nerve injury F1 group showed the best results suggesting recovery acceleration; at 8th week F1 and LLLT&F1 groups presented better features and higher vascularization that could be associated with VEGF maintenance.

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<![CDATA[Function and energy consumption constrain neuronal biophysics in a canonical computation: Coincidence detection]]> https://www.researchpad.co/article/5c12cf09d5eed0c484913d9f

Neural morphology and membrane properties vary greatly between cell types in the nervous system. The computations and local circuit connectivity that neurons support are thought to be the key factors constraining the cells’ biophysical properties. Nevertheless, additional constraints can be expected to further shape neuronal design. Here, we focus on a particularly energy-intense system (as indicated by metabolic markers): principal neurons in the medial superior olive (MSO) nucleus of the auditory brainstem. Based on a modeling approach, we show that a trade-off between the level of performance of a functionally relevant computation and energy consumption predicts optimal ranges for cell morphology and membrane properties. The biophysical parameters appear most strongly constrained by functional needs, while energy use is minimized as long as function can be maintained. The key factors that determine model performance and energy consumption are 1) the saturation of the synaptic conductance input and 2) the temporal resolution of the postsynaptic signals as they reach the soma, which is largely determined by active membrane properties. MSO cells seem to operate close to pareto optimality, i.e., the trade-off boundary between performance and energy consumption that is formed by the set of optimal models. Good performance for drastically lower costs could in theory be achieved by small neurons without dendrites, as seen in the avian auditory system, pointing to additional constraints for mammalian MSO cells, including their circuit connectivity.

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<![CDATA[The neuroanatomy of the siboglinid Riftia pachyptila highlights sedentarian annelid nervous system evolution]]> https://www.researchpad.co/article/5c1c0ab1d5eed0c4844268d5

Tracing the evolution of the siboglinid group, peculiar group of marine gutless annelids, requires the detailed study of the fragmentarily explored central nervous system of vestimentiferans and other siboglinids. 3D reconstructions of the neuroanatomy of Riftia revealed that the “brain” of adult vestimentiferans is a fusion product of the supraesophageal and subesophageal ganglia. The supraesophageal ganglion-like area contains the following neural structures that are homologous to the annelid elements: the peripheral perikarya of the brain lobes, two main transverse commissures, mushroom-like structures, commissural cell cluster, and the circumesophageal connectives with two roots which give rise to the palp neurites. Three pairs of giant perikarya are located in the supraesophageal ganglion, giving rise to the paired giant axons. The circumesophageal connectives run to the VNC. The subesophageal ganglion-like area contains a tripartite ventral aggregation of perikarya (= the postoral ganglion of the VNC) interconnected by the subenteral commissure. The paired VNC is intraepidermal, not ganglionated over most of its length, associated with the ciliary field, and comprises the giant axons. The pairs of VNC and the giant axons fuse posteriorly. Within siboglinids, the vestimentiferans are distinguished by a large and considerably differentiated brain. This reflects the derived development of the tentacle crown. The tentacles of vestimentiferans are homologous to the annelid palps based on their innervation from the dorsal and ventral roots of the circumesophageal connectives. Neuroanatomy of the vestimentiferan brains is close to the brains of Cirratuliiformia and Spionida/Sabellida, which have several transverse commissures, specific position of the giant somata (if any), and palp nerve roots (if any). The palps and palp neurite roots originally developed in all main annelid clades (basally branching, errantian and sedentarian annelids), show the greatest diversity in their number in sedentarian species. Over the course of evolution of Sedentaria, the number of palps and their nerve roots either dramatically increased (as in vestimentiferan siboglinids) or were lost.

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<![CDATA[Compartment models for the electrical stimulation of retinal bipolar cells]]> https://www.researchpad.co/article/5c215132d5eed0c4843f91fe

Bipolar cells of the retina are among the smallest neurons of the nervous system. For this reason, compared to other neurons, their delay in signaling is minimal. Additionally, the small bipolar cell surface combined with the low membrane conductance causes very little attenuation in the signal from synaptic input to the terminal. The existence of spiking bipolar cells was proven over the last two decades, but until now no complete model including all important ion channel types was published. The present study amends this and analyzes the impact of the number of model compartments on simulation accuracy. Characteristic features like membrane voltages and spike generation were tested and compared for one-, two-, four- and 117-compartment models of a macaque bipolar cell. Although results were independent of the compartment number for low membrane conductances (passive membranes), nonlinear regimes such as spiking required at least a separate axon compartment. At least a four compartment model containing the functionally different segments dendrite, soma, axon and terminal was needed for understanding signaling in spiking bipolar cells. Whereas for intracellular current application models with small numbers of compartments showed quantitatively correct results in many cases, the cell response to extracellular stimulation is sensitive to spatial variation of the electric field and accurate modeling therefore demands for a large number of short compartments even for passive membranes.

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<![CDATA[A stochastic framework to model axon interactions within growing neuronal populations]]> https://www.researchpad.co/article/5c0ed74ed5eed0c484f13eaa

The confined and crowded environment of developing brains imposes spatial constraints on neuronal cells that have evolved individual and collective strategies to optimize their growth. These include organizing neurons into populations extending their axons to common target territories. How individual axons interact with each other within such populations to optimize innervation is currently unclear and difficult to analyze experimentally in vivo. Here, we developed a stochastic model of 3D axon growth that takes into account spatial environmental constraints, physical interactions between neighboring axons, and branch formation. This general, predictive and robust model, when fed with parameters estimated on real neurons from the Drosophila brain, enabled the study of the mechanistic principles underlying the growth of axonal populations. First, it provided a novel explanation for the diversity of growth and branching patterns observed in vivo within populations of genetically identical neurons. Second, it uncovered that axon branching could be a strategy optimizing the overall growth of axons competing with others in contexts of high axonal density. The flexibility of this framework will make it possible to investigate the rules underlying axon growth and regeneration in the context of various neuronal populations.

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<![CDATA[Full reconstruction of large lobula plate tangential cells in Drosophila from a 3D EM dataset]]> https://www.researchpad.co/article/5c08419cd5eed0c484fca32f

With the advent of neurogenetic methods, the neural basis of behavior is presently being analyzed in more and more detail. This is particularly true for visually driven behavior of Drosophila melanogaster where cell-specific driver lines exist that, depending on the combination with appropriate effector genes, allow for targeted recording, silencing and optogenetic stimulation of individual cell-types. Together with detailed connectomic data of large parts of the fly optic lobe, this has recently led to much progress in our understanding of the neural circuits underlying local motion detection. However, how such local information is combined by optic flow sensitive large-field neurons is still incompletely understood. Here, we aim to fill this gap by a dense reconstruction of lobula plate tangential cells of the fly lobula plate. These neurons collect input from many hundreds of local motion-sensing T4/T5 neurons and connect them to descending neurons or central brain areas. We confirm all basic features of HS and VS cells as published previously from light microscopy. In addition, we identified the dorsal and the ventral centrifugal horizontal, dCH and vCH cell, as well as three VSlike cells, including their distinct dendritic and axonal projection area.

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<![CDATA[Evaluation of optic nerve subarachnoid space in primary open angle glaucoma using ultrasound examination]]> https://www.researchpad.co/article/5c0841f8d5eed0c484fcb518

Objectives

To measure Optic Nerve Subarachnoid Space (ONSAS) in patients with primary open-angle glaucoma (POAG) and controls using A-scan ultrasound and to evaluate the measurement of the ONSAS in relation to age patient and OCT parameters.

Methods

This retrospective study included 53 consecutive eyes of 27 patients with POAG and 64 normal eyes of 32 controls. Both glaucomatous and control groups were divided into 2 subgroups according to age: <60 age (glaucomatous and control group 1) and 61–90 age (glaucomatous and control group 2).

Results

The ONSAS was significantly lower in all glaucomatous eyes (3.54 ± 0.38) versus normal eyes (3.87 ± 0.32) (p = 0.001). Significant reduction of ONSAS was showed in control group 2 (3.63 mm ± 0.37) compared to control group 1 (3.87 mm ± 0.32) (p = 0.014) and between glaucoma group 1 (3.54 mm ± 0.38) and control group 1 (p = 0.001). While no significant differences were observed between glaucomatous group 2 (3.48 mm ± 0.41) and control group 2 (p = 0.17) and between glaucoma group 1 and glaucoma group 2 (p = 0.609). Lastly, the ONSAS was not significantly associated with GCC and RNFL parameters except for Focal Loss Volume (FLV), Superior RNFL and ONSAS in glaucoma group 1 and for FLV and ONSAS in all glaucomatous group.

Conclusion

Standardized A-scan ultrasound is a non invasive imaging technique with which it is possible to monitor ONSAS changes in glaucomatous patients. The reduction of ONSAS confirm the importance of the lower orbital CSFP as further risk factor in the progression of glaucoma disease.

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<![CDATA[Lactosylceramide synthases encoded by B4galt5 and 6 genes are pivotal for neuronal generation and myelin formation in mice]]> https://www.researchpad.co/article/5b8b29d640307c405292ca4e

It is uncertain which β4-galactosyltransferase (β4GalT; gene name, B4galt), β4GalT-5 and/or β4GalT-6, is responsible for the production of lactosylceramide (LacCer) synthase, which functions in the initial step of ganglioside biosynthesis. Here, we generated conditional B4galt5 knockout (B4galt5 cKO) mice, using Nestin-Cre mice, and crossed these with B4galt6 KO mice to generate B4galt5 and 6 double KO (DKO) mice in the central nervous system (CNS). LacCer synthase activity and major brain gangliosides were completely absent in brain homogenates from the DKO mice, although LacCer synthase activity was about half its normal level in B4galt5 cKO mice and B4galt6 KO mice. The DKO mice were born normally but they showed growth retardation and motor deficits at 2 weeks and died by 4 weeks of age. Histological analyses showed that myelin-associated proteins were rarely found localized in axons in the cerebral cortex, and axonal and myelin formation were remarkably impaired in the spinal cords of the DKO mice. Neuronal cells, differentiated from neurospheres that were prepared from the DKO mice, showed impairments in neurite outgrowth and branch formation, which can be explained by the fact that neurospheres from DKO mice could weakly interact with laminin due to lack of gangliosides, such as GM1a. Furthermore, the neurons were immature and perineuronal nets (PNNs) were poorly formed in DKO cerebral cortices. Our results indicate that LacCer synthase is encoded by B4galt5 and 6 genes in the CNS, and that gangliosides are indispensable for neuronal maturation, PNN formation, and axonal and myelin formation.

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<![CDATA[The effects of aging on neuropil structure in mouse somatosensory cortex—A 3D electron microscopy analysis of layer 1]]> https://www.researchpad.co/article/5b4a08df463d7e3fbe689132

This study has used dense reconstructions from serial EM images to compare the neuropil ultrastructure and connectivity of aged and adult mice. The analysis used models of axons, dendrites, and their synaptic connections, reconstructed from volumes of neuropil imaged in layer 1 of the somatosensory cortex. This shows the changes to neuropil structure that accompany a general loss of synapses in a well-defined brain region. The loss of excitatory synapses was balanced by an increase in their size such that the total amount of synaptic surface, per unit length of axon, and per unit volume of neuropil, stayed the same. There was also a greater reduction of inhibitory synapses than excitatory, particularly those found on dendritic spines, resulting in an increase in the excitatory/inhibitory balance. The close correlations, that exist in young and adult neurons, between spine volume, bouton volume, synaptic size, and docked vesicle numbers are all preserved during aging. These comparisons display features that indicate a reduced plasticity of cortical circuits, with fewer, more transient, connections, but nevertheless an enhancement of the remaining connectivity that compensates for a generalized synapse loss.

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<![CDATA[A subset of octopaminergic neurons that promotes feeding initiation in Drosophila melanogaster]]> https://www.researchpad.co/article/5b49f0ba463d7e3adec7b982

Octopamine regulates feeding behavioral responses in Drosophila melanogaster, however the molecular and circuit mechanisms have not been fully elucidated. Here, we investigated the role of a subset of octopaminergic neurons, the OA-VPM4 cluster, in sucrose acceptance behavior. Thermogenetic activation of Gal4 lines containing OA-VPM4 promoted proboscis extension to sucrose, while optogenetic inactivation reduced extension. Anatomically, the presynaptic terminals of OA-VPM4 are in close proximity to the axons of sugar-responsive gustatory sensory neurons. Moreover, RNAi knockdown of a specific class of octopamine receptor, OAMB, selectively in sugar-sensing gustatory neurons decreased the behavioral response to sucrose. By calcium imaging experiments, we found that application of octopamine potentiates sensory responses to sucrose in satiated flies. Taken together, these findings suggest a model by which OA-VPM4 promotes feeding behavior by modulating the activity of sensory neurons.

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<![CDATA[Macular choroidal thickness and peripapillary retinal nerve fiber layer thickness in normal adults and patients with optic atrophy due to acute idiopathic demyelinating optic neuritis]]> https://www.researchpad.co/article/5b28b401463d7e129299938e

Purpose

To evaluate the association between macular choroidal thickness and peripapillary RNFL thickness in patients with optic atrophy due to acute idiopathic demyelinating optic neuritis and in normal controls using spectral domain optical coherence tomography (SD-OCT).

Methods

We performed SD-OCT peripapillary RNFL circular scan centered on the optic disc with horizontal and vertical crosshair scans through the fovea using the enhanced depth technique in 62 eyes with optic atrophy due to acute idiopathic demyelinating optic neuritis and 86 eyes of normal controls. The association between RNFL thickness and macular choroidal thickness measurements was assessed.

Results

The mean age was 43 ± 14 years (mean ± SD) in patients with optic atrophy and 45 ± 16 years in healthy controls (p = 0.791). There was a significant association between nasal peripapillary RNFL thickness and choroidal thickness at 3.0 mm nasal to the foveal center in patients with optic atrophy in multivariate analysis (estimate = 1.398, p = 0.011). In controls, there were significant associations between global average, superior, and inferior peripapillary RNFL thickness and choroidal thickness at 3.0 mm superior to the foveal center (estimate = -60.112, p = 0.044, estimate = 15.821, p = 7.312, and estimate = 15.203, p = 7.222, respectively).

Conclusions

Our SD-OCT data revealed that there was a significant association between peripapillary RNFL thickness and macular choroidal thickness in patients with optic atrophy due to acute idiopathic demyelinating optic neuritis and in controls, although the mechanism remained unclear. The difference in the pattern of association between patients with optic atrophy and controls suggests that optic atrophy caused by acute idiopathic demyelinating optic neuritis could affect the pattern of association between peripapillary RNFL thickness and macular choroidal thickness.

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<![CDATA[Receptors of intermediates of carbohydrate metabolism, GPR91 and GPR99, mediate axon growth]]> https://www.researchpad.co/article/5b07d0e7463d7e0d4a37a6ed

During the development of the visual system, high levels of energy are expended propelling axons from the retina to the brain. However, the role of intermediates of carbohydrate metabolism in the development of the visual system has been overlooked. Here, we report that the carbohydrate metabolites succinate and α-ketoglutarate (α-KG) and their respective receptor—GPR91 and GPR99—are involved in modulating retinal ganglion cell (RGC) projections toward the thalamus during visual system development. Using ex vivo and in vivo approaches, combined with pharmacological and genetic analyses, we revealed that GPR91 and GPR99 are expressed on axons of developing RGCs and have complementary roles during RGC axon growth in an extracellular signal–regulated kinases 1 and 2 (ERK1/2)-dependent manner. However, they have no effects on axon guidance. These findings suggest an important role for these receptors during the establishment of the visual system and provide a foundational link between carbohydrate metabolism and axon growth.

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