Alien Registration- Soucy, Fred F. (Bangor, Penobscot County)

https://digitalmaine.com/alien_docs/10526/thumbnail.jp

Gaze-stabilizing central vestibular neurons project asymmetrically to extraocular motoneuron pools.

Within reflex circuits, specific anatomical projections allow central neurons to relay sensations to effectors that generate movements. A major challenge is to relate anatomical features of central neural populations -- such as asymmetric connectivity -- to the computations the populations perform. To address this problem, we mapped the anatomy, modeled the function, and discovered a new behavioral role for a genetically-defined population of central vestibular neurons in rhombomeres 5-7 of larval zebrafish. First, we found that neurons within this central population project preferentially to motoneurons that move the eyes downward. Concordantly, when the entire population of asymmetrically-projecting neurons was stimulated collectively, only downward eye rotations were observed, demonstrating a functional correlate of the anatomical bias. When these neurons are ablated, fish failed to rotate their eyes following either nose-up or nose-down body tilts. This asymmetrically-projecting central population thus participates in both up and downward gaze stabilization. In addition to projecting to motoneurons, central vestibular neurons also receive direct sensory input from peripheral afferents. To infer whether asymmetric projections can facilitate sensory encoding or motor output, we modeled differentially-projecting sets of central vestibular neurons. Whereas motor command strength was independent of projection allocation, asymmetric projections enabled more accurate representation of nose-up stimuli. The model shows how asymmetric connectivity could enhance the representation of imbalance during nose-up postures while preserving gaze-stabilization performance. Finally, we found that central vestibular neurons were necessary for a vital behavior requiring maintenance of a nose-up posture: swim bladder inflation. These observations suggest that asymmetric connectivity in the vestibular system facilitates representation of ethologically-relevant stimuli without compromising reflexive behavior.SIGNIFICANCE STATEMENTInterneuron populations use specific anatomical projections to transform sensations into reflexive actions. Here we examined how the anatomical composition of a genetically-defined population of balance interneurons in the larval zebrafish relates to the computations it performs. First, we found that the population of interneurons that stabilize gaze preferentially project to motoneurons that move the eyes downward. Next, we discovered through modeling that such projection patterns can enhance the encoding of nose-up sensations without compromising gaze stabilization. Finally we found that loss of these interneurons impairs a vital behavior, swim bladder inflation, that relies on maintaining a nose-up posture. These observations suggest that anatomical specialization permits neural circuits to represent relevant features of the environment without compromising behavior

Honesty mediates the relationship between serotonin and reaction to unfairness

How does one deal with unfair behaviors? This subject has long been investigated by various disciplines including philosophy, psychology, economics, and biology. However, our reactions to unfairness differ from one individual to another. Experimental economics studies using the ultimatum game (UG), in which players must decide whether to accept or reject fair or unfair offers, have also shown that there are substantial individual differences in reaction to unfairness. However, little is known about psychological as well as neurobiological mechanisms of this observation. We combined a molecular imaging technique, an economics game, and a personality inventory to elucidate the neurobiological mechanism of heterogeneous reactions to unfairness. Contrary to the common belief that aggressive personalities (impulsivity or hostility) are related to the high rejection rate of unfair offers in UG, we found that individuals with apparently peaceful personalities (straightforwardness and trust) rejected more often and were engaged in personally costly forms of retaliation. Furthermore, individuals with a low level of serotonin transporters in the dorsal raphe nucleus (DRN) are honest and trustful, and thus cannot tolerate unfairness, being candid in expressing their frustrations. In other words, higher central serotonin transmission might allow us to behave adroitly and opportunistically, being good at playing games while pursuing self-interest. We provide unique neurobiological evidence to account for individual differences of reaction to unfairness

Neuropeptidergic Signaling Partitions Arousal Behaviors in Zebrafish

Animals modulate their arousal state to ensure that their sensory responsiveness and locomotor activity match environmental demands. Neuropeptides can regulate arousal, but studies of their roles in vertebrates have been constrained by the vast array of neuropeptides and their pleiotropic effects. To overcome these limitations, we systematically dissected the neuropeptidergic modulation of arousal in larval zebrafish. We quantified spontaneous locomotor activity and responsiveness to sensory stimuli after genetically induced expression of seven evolutionarily conserved neuropeptides, including adenylate cyclase activating polypeptide 1b (adcyap1b), cocaine-related and amphetamine-related transcript (cart), cholecystokinin (cck), calcitonin gene-related peptide (cgrp), galanin, hypocretin, and nociceptin. Our study reveals that arousal behaviors are dissociable: neuropeptide expression uncoupled spontaneous activity from sensory responsiveness, and uncovered modality-specific effects upon sensory responsiveness. Principal components analysis and phenotypic clustering revealed both shared and divergent features of neuropeptidergic functions: hypocretin and cgrp stimulated spontaneous locomotor activity, whereas galanin and nociceptin attenuated these behaviors. In contrast, cart and adcyap1b enhanced sensory responsiveness yet had minimal impacts on spontaneous activity, and cck expression induced the opposite effects. Furthermore, hypocretin and nociceptin induced modality-specific differences in responsiveness to changes in illumination. Our study provides the first systematic and high-throughput analysis of neuropeptidergic modulation of arousal, demonstrates that arousal can be partitioned into independent behavioral components, and reveals novel and conserved functions of neuropeptides in regulating arousal

Abnormal metabolic network activity in REM sleep behavior disorder

OBJECTIVE: To determine whether the Parkinson disease-related covariance pattern (PDRP) expression is abnormally increased in idiopathic REM sleep behavior disorder (RBD) and whether increased baseline activity is associated with greater individual risk of subsequent phenoconversion. METHODS: For this cohort study, we recruited 2 groups of RBD and control subjects. Cohort 1 comprised 10 subjects with RBD (63.5 +/- 9.4 years old) and 10 healthy volunteers (62.7 +/- 8.6 years old) who underwent resting-state metabolic brain imaging with (18)F-fluorodeoxyglucose PET. Cohort 2 comprised 17 subjects with RBD (68.9 +/- 4.8 years old) and 17 healthy volunteers (66.6 +/- 6.0 years old) who underwent resting brain perfusion imaging with ethylcysteinate dimer SPECT. The latter group was followed clinically for 4.6 +/- 2.5 years by investigators blinded to the imaging results. PDRP expression was measured in both RBD groups and compared with corresponding control values. RESULTS: PDRP expression was elevated in both groups of subjects with RBD (cohort 1: p \u3c 0.04; cohort 2: p \u3c 0.005). Of the 17 subjects with long-term follow-up, 8 were diagnosed with Parkinson disease or dementia with Lewy bodies; the others did not phenoconvert. For individual subjects with RBD, final phenoconversion status was predicted using a logistical regression model based on PDRP expression and subject age at the time of imaging (r(2) = 0.64, p \u3c 0.0001). CONCLUSIONS: Latent network abnormalities in subjects with idiopathic RBD are associated with a greater likelihood of subsequent phenoconversion to a progressive neurodegenerative syndrome

MYOD1 involvement in myopathy

[Excerpt] Introduction Myogenic Differentiation 1 (MYOD1) encodes a transcription factor that plays an important role in myogenic determination into mature skeletal muscle [1]. The first loss-of-function mutation of MYOD1 in humans was described in three siblings with perinatal lethal fetal akinesia [2].[...]We thank the individual and family. Funding was provided by The Fonds de recherche du Québec - Santé (FRQS) and Canadian Institutes of Health Research (CIHR) to P.M.C., Fundação para a Ciência e Tecnologia (FCT) with the fellowship SFRH/BD/84650/2010 to F.L. and Groupe Pasteur Mutualité Foundation (GPM Foundation) to M.M.info:eu-repo/semantics/publishedVersio

Refining the phenotype associated with biallelic DNAJC21 mutations

Accepted manuscriptInherited bone marrow failure syndromes (IBMFS) are caused by mutations in genes involved in genomic stability. Although they may be recognized by the association of typical clinical features, variable penetrance and expressivity are common, and clinical diagnosis is often challenging. DNAJC21, which is involved in ribosome biogenesis, was recently linked to bone marrow failure. However, the specific phenotype and natural history remain to be defined. We correlate molecular data, phenotype, and clinical history of 5 unreported affected children and all individuals reported in the literature. All patients present features consistent with IBMFS: bone marrow failure, growth retardation, failure to thrive, developmental delay, recurrent infections, and skin, teeth or hair abnormalities. Additional features present in some individuals include retinal abnormalities, pancreatic insufficiency, liver cirrhosis, skeletal abnormalities, congenital hip dysplasia, joint hypermobility, and cryptorchidism. We suggest that DNAJC21-related diseases constitute a distinct IBMFS, with features overlapping Shwachman-Diamond syndrome and Dyskeratosis congenita, and additional characteristics that are specific to DNAJC21 mutations. The full phenotypic spectrum, natural history, and optimal management will require more reports. Considering the aplastic anemia, the possible increased risk for leukemia, and the multisystemic features, we provide a checklist for clinical evaluation at diagnosis and regular follow-up.FCT—Fundação para a Ciência e a Tecnologia (SFRH/BD/84650/2010)info:eu-repo/semantics/publishedVersio

Olfactory marker protein (OMP) regulates formation and refinement of the olfactory glomerular map

Inputs from olfactory sensory neuron (OSN) axons expressing the same type of odorant receptor (OR) converge in the glomerulus of the main olfactory bulb. A key marker of mature OSNs is olfactory marker protein (OMP), whose deletion has been associated with deficits in OSN signal transduction and odor discrimination. Here, we investigate glomerular odor responses and anatomical architecture in mice in which one or both alleles of OMP are replaced by the fluorescent synaptic activity reporter, synaptopHluorin. Functionally heterogeneous glomeruli, that is, ones with microdomains with distinct odor responses, are rare in OMP(+/-) mice, but occur frequently in OMP(-/-) mice. Genetic targeting of single ORs reveals that these microdomains arise from co-innervation of individual glomeruli by OSNs expressing different ORs. This glomerular mistargeting is locally restricted to a few glomerular diameters. Our studies document functional heterogeneity in sensory input within individual glomeruli and uncover its anatomical correlate, revealing an unexpected role for OMP in the formation and refinement of the glomerular map

Computational exploration of molecular receptive fields in the olfactory bulb reveals a glomerulus-centric chemical map

© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Progress in olfactory research is currently hampered by incomplete knowledge about chemical receptive ranges of primary receptors. Moreover, the chemical logic underlying the arrangement of computational units in the olfactory bulb has still not been resolved. We undertook a large-scale approach at characterising molecular receptive ranges (MRRs) of glomeruli in the dorsal olfactory bulb (dOB) innervated by the MOR18-2 olfactory receptor, also known as Olfr78, with human ortholog OR51E2. Guided by an iterative approach that combined biological screening and machine learning, we selected 214 odorants to characterise the response of MOR18-2 and its neighbouring glomeruli. We found that a combination of conventional physico-chemical and vibrational molecular descriptors performed best in predicting glomerular responses using nonlinear Support-Vector Regression. We also discovered several previously unknown odorants activating MOR18-2 glomeruli, and obtained detailed MRRs of MOR18-2 glomeruli and their neighbours. Our results confirm earlier findings that demonstrated tunotopy, that is, glomeruli with similar tuning curves tend to be located in spatial proximity in the dOB. In addition, our results indicate chemotopy, that is, a preference for glomeruli with similar physico-chemical MRR descriptions being located in spatial proximity. Together, these findings suggest the existence of a partial chemical map underlying glomerular arrangement in the dOB. Our methodology that combines machine learning and physiological measurements lights the way towards future high-throughput studies to deorphanise and characterise structure-activity relationships in olfaction.Peer reviewe

LED Arrays as Cost Effective and Efficient Light Sources for Widefield Microscopy

New developments in fluorophores as well as in detection methods have fueled the rapid growth of optical imaging in the life sciences. Commercial widefield microscopes generally use arc lamps, excitation/emission filters and shutters for fluorescence imaging. These components can be expensive, difficult to maintain and preclude stable illumination. Here, we describe methods to construct inexpensive and easy-to-use light sources for optical microscopy using light-emitting diodes (LEDs). We also provide examples of its applicability to biological fluorescence imaging