scholarly journals Two brain pathways initiate distinct forward walking programs in Drosophila

2019 ◽  
Author(s):  
Salil S. Bidaye ◽  
Meghan Laturney ◽  
Amy K. Chang ◽  
Yuejiang Liu ◽  
Till Bockemühl ◽  
...  
Keyword(s):  
High Velocity ◽  
Projection Neurons ◽  
Descending Neurons ◽  
Specific Manner ◽  
Visual Projection ◽  
Brain Pathways ◽  
Walking Programs ◽  
Context Specific ◽  
The Brain ◽  
Insight Into

SummaryAn animal at rest or engaged in stationary behaviors can instantaneously initiate goal-directed walking. How descending brain inputs trigger rapid transitions from a non-walking state to an appropriate walking state is unclear. Here, we identify two specific neuronal classes in the Drosophila brain that drive two distinct forward walking programs in a context-specific manner. The first class, named P9, consists of descending neurons that drive forward walking with ipsilateral turning. P9 receives inputs from central courtship-promoting neurons and visual projection neurons and is necessary for a male to track a female during courtship. The second class comprises novel, higher order neurons, named BPN, that drives straight, forward walking. BPN is required for high velocity walking and is active during long, fast, straight walking bouts. Thus, this study reveals separate brain pathways for object-directed steering and fast straight walking, providing insight into how the brain initiates different walking programs.

scholarly journals Neurexophilin4 is a selectively expressed α-neurexin ligand that modulates specific cerebellar synapses and motor functions

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Xiangling Meng ◽  
Christopher M McGraw ◽  
Wei Wang ◽  
Junzhan Jing ◽  
Szu-Ying Yeh ◽  
...  
Keyword(s):  
Motor Control ◽  
Cell Adhesion ◽  
Motor Learning ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Partial Explanation ◽  
Specific Manner ◽  
Context Specific ◽  
And Function ◽  
The Brain

Neurexophilins are secreted neuropeptide-like glycoproteins, and neurexophilin1 and neurexophilin3 are ligands for the presynaptic cell adhesion molecule α-neurexin. Neurexophilins are more selectively expressed in the brain than α-neurexins, however, which led us to ask whether neurexophilins modulate the function of α-neurexin in a context-specific manner. We characterized the expression and function of neurexophilin4 in mice and found it to be expressed in subsets of neurons responsible for feeding, emotion, balance, and movement. Deletion of Neurexophilin4 caused corresponding impairments, most notably in motor learning and coordination. We demonstrated that neurexophilin4 interacts with α-neurexin and GABAARs in the cerebellum. Loss of Neurexophilin4 impaired cerebellar Golgi-granule inhibitory neurotransmission and synapse number, providing a partial explanation for the motor learning and coordination deficits observed in the Neurexophilin4 null mice. Our data illustrate how selectively expressed Neurexophilin4, an α-neurexin ligand, regulates specific synapse function and modulates cerebellar motor control.

Effects of the SNAP25 on Integration Ability of Brain Functions in Children With ADHD

2020 ◽  
pp. 108705472096456
Author(s):  
Yue Yang ◽  
Gang Peng ◽  
Hongwu Zeng ◽  
Diangang Fang ◽  
Linlin Zhang ◽  
...  
Keyword(s):  
Time Window ◽  
Precentral Gyrus ◽  
Children With Adhd ◽  
Brain Functions ◽  
Lingual Gyrus ◽  
Window Method ◽  
Central Gyrus ◽  
The Right ◽  
The Brain ◽  
Insight Into

Objective: The present study aimed to examine the effects of SNAP25 on the integration ability of intrinsic brain functions in children with ADHD, and whether the integration ability was associated with working memory (WM). Methods: A sliding time window method was used to calculate the spatial and temporal concordance among five rs-fMRI regional indices in 55 children with ADHD and 20 healthy controls. Results: The SNAP25 exhibited significant interaction effects with ADHD diagnosis on the voxel-wise concordance in the right posterior central gyrus, fusiform gyrus and lingual gyrus. Specifically, for children with ADHD, G-carriers showed increased voxel-wise concordance in comparison to TT homozygotes in the right precentral gyrus, superior frontal gyrus, postcentral gyrus, and middle frontal gyrus. The voxel-wise concordance was also found to be related to WM. Conclusion: Our findings provided a new insight into the neural mechanisms of the brain function of ADHD children.

scholarly journals Pain Detection and the Privacy of Subjective Experience

2007 ◽  
Vol 33 (2-3) ◽  
pp. 433-456 ◽  
Author(s):  
Adam J. Kolber
Keyword(s):  
Subjective Experience ◽  
Brain Regions ◽  
Physical Pain ◽  
Medical Evidence ◽  
Functional Magnetic Resonance ◽  
Positron Emission ◽  
Pain Symptoms ◽  
The Brain ◽  
Insight Into ◽  
Neuroimaging Techniques

A neurologist with abdominal pain goes to see a gastroenterologist for treatment. The gastroenterologist asks the neurologist where it hurts. The neurologist replies, “In my head, of course.” Indeed, while we can feel pain throughout much of our bodies, pain signals undergo most of their processing in the brain. Using neuroimaging techniques like functional magnetic resonance imaging (“fMRI”) and positron emission tomography (“PET”), researchers have more precisely identified brain regions that enable us to experience physical pain. Certain regions of the brain's cortex, for example, increase in activation when subjects are exposed to painful stimuli. Furthermore, the amount of activation increases with the intensity of the painful stimulus. These findings suggest that we may be able to gain insight into the amount of pain a particular person is experiencing by non-invasively imaging his brain.Such insight could be particularly valuable in the courtroom where we often have no definitive medical evidence to prove or disprove claims about the existence and extent of pain symptoms.

scholarly journals Distinct Roles of Deiodinases on the Phenotype of Mct8 Defect: A Comparison of Eight Different Mouse Genotypes

Endocrinology ◽  
2011 ◽  
Vol 152 (3) ◽  
pp. 1180-1191 ◽  
Author(s):  
Xiao-Hui Liao ◽  
Caterina Di Cosmo ◽  
Alexandra M. Dumitrescu ◽  
Arturo Hernandez ◽  
Jacqueline Van Sande ◽  
...  
Keyword(s):  
Growth Response ◽  
Pituitary Thyroid Axis ◽  
Severe Impairment ◽  
Serum T3 ◽  
Serum T4 ◽  
Thyroid Axis ◽  
Mct8 Deficiency ◽  
The Brain ◽  
Insight Into ◽  
Serum Tsh

Mice deficient in the thyroid hormone (TH) transporter Mct8 (Mct8KO) have increased 5′-deiodination and impaired TH secretion and excretion. These and other unknown mechanisms result in the low-serum T4, high T3, and low rT3 levels characteristic of Mct8 defects. We investigated to what extent each of the 5′-deiodinases (D1, D2) contributes to the serum TH abnormalities of the Mct8KO by generating mice with all combinations of Mct8 and D1 and/or D2 deficiencies and comparing the resulting eight genotypes. Adding D1 deficiency to that of Mct8 corrected the serum TH abnormalities of Mct8KO mice, normalized brain T3 content, and reduced the impaired expression of TH-responsive genes. In contrast, Mct8D2KO mice maintained the serum TH abnormalities of Mct8KO mice. However, the serum TSH level increased 27-fold, suggesting a severely impaired hypothalamo-pituitary-thyroid axis. The brain of Mct8D2KO manifested a pattern of more severe impairment of TH action than Mct8KO alone. In triple Mct8D1D2KO mice, the markedly increased serum TH levels produced milder brain defect than that of Mct8D2KO at the expense of more severe liver thyrotoxicosis. Additionally, we observed that mice deficient in D2 had an unexplained marked reduction in the thyroid growth response to TSH. Our studies on these eight genotypes provide a unique insight into the complex interplay of the deiodinases in the Mct8 defect and suggest that D1 contributes to the increased serum T3 in Mct8 deficiency, whereas D2 mainly functions locally, converting T4 to T3 to compensate for distinct cellular TH depletion in Mct8KO mice.

Differential Involvement of Projection Neurons During Emergence of Spontaneous Activity in the Developing Avian Hindbrain

2009 ◽  
Vol 101 (2) ◽  
pp. 591-602 ◽  
Author(s):  
Hiraku Mochida ◽  
Gilles Fortin ◽  
Jean Champagnat ◽  
Joel C. Glover
Keyword(s):  
Spontaneous Activity ◽  
Projection Neuron ◽  
Projection Neurons ◽  
Charge Coupled Device ◽  
Neuron Populations ◽  
Motor Nerves ◽  
Differential Involvement ◽  
A Charge ◽  
The Brain ◽  
Calcium Green

To better characterize the emergence of spontaneous neuronal activity in the developing hindbrain, spontaneous activity was recorded optically from defined projection neuron populations in isolated preparations of the brain stem of the chicken embryo. Ipsilaterally projecting reticulospinal (RS) neurons and several groups of vestibuloocular (VO) neurons were labeled retrogradely with Calcium Green-1 dextran amine and spontaneous calcium transients were recorded using a charge-coupled-device camera mounted on a fluorescence microscope. Simultaneous extracellular recordings were made from one of the trigeminal motor nerves (nV) to register the occurrence of spontaneous synchronous bursts of activity. Two types of spontaneous activity were observed: synchronous events (SEs), which occurred in register with spontaneous bursts in nV once every few minutes and were tetrodotoxin (TTX) dependent, and asynchronous events (AEs), which occurred in the intervals between SEs and were TTX resistant. AEs occurred developmentally before SEs and were in general smaller and more variable in amplitude than SEs. SEs appeared at the same stage as nV bursts early on embryonic day 4, first in RS neurons and then in VO neurons. All RS neurons participated equally in SEs from the outset, whereas different subpopulations of VO neurons participated differentially, both in terms of the proportion of neurons that exhibited SEs, the fidelity with which the SEs in individual neurons followed the nV bursts, and the developmental stage at which SEs appeared and matured. The results show that spontaneous activity is expressed heterogeneously among hindbrain projection neuron populations, suggesting its differential involvement in the formation of different functional neuronal circuits.

scholarly journals Diving into the world of alcohol teratogenesis: a review of zebrafish models of fetal alcohol spectrum disorder

2018 ◽  
Vol 96 (2) ◽  
pp. 88-97 ◽  
Author(s):  
Yohaan Fernandes ◽  
Desire M. Buckley ◽  
Johann K. Eberhart
Keyword(s):  
Fetal Alcohol Spectrum Disorder ◽  
Model Organism ◽  
Spectrum Disorder ◽  
Structural Defects ◽  
Craniofacial Skeleton ◽  
Fetal Alcohol ◽  
Embryonic Exposure ◽  
Fetal Alcohol Spectrum ◽  
The Brain ◽  
Insight Into

The term fetal alcohol spectrum disorder (FASD) refers to the entire suite of deleterious outcomes resulting from embryonic exposure to alcohol. Along with other reviews in this special issue, we provide insight into how animal models, specifically the zebrafish, have informed our understanding of FASD. We first provide a brief introduction to FASD. We discuss the zebrafish as a model organism and its strengths for alcohol research. We detail how zebrafish has been used to model some of the major defects present in FASD. These include behavioral defects, such as social behavior as well as learning and memory, and structural defects, disrupting organs such as the brain, sensory organs, heart, and craniofacial skeleton. We provide insights into how zebrafish research has aided in our understanding of the mechanisms of ethanol teratogenesis. We end by providing some relatively recent advances that zebrafish has provided in characterizing gene-ethanol interactions that may underlie FASD.

scholarly journals Reflections on the Constraints and Opportunities in Therapy in Rett Syndrome

2006 ◽  
Vol 6 ◽  
pp. 992-997 ◽  
Author(s):  
Alison M. Kerr
Keyword(s):  
Quality Of Life ◽  
Neural Networks ◽  
Rett Syndrome ◽  
Clear Understanding ◽  
Research Experience ◽  
Hormonal Responses ◽  
Physical Limitations ◽  
The Brain ◽  
Insight Into

More than 20 years of clinical and research experience with affected people in the British Isles has provided insight into particular challenges for therapists, educators, or parents wishing to facilitate learning and to support the development of skills in people with Rett syndrome. This paper considers the challenges in two groups: those due to constraints imposed by the disabilities associated with the disorder and those stemming from the opportunities, often masked by the disorder, allowing the development of skills that depend on less-affected areas of the brain. Because the disorder interferes with the synaptic links between neurones, the functions of the brain that are most dependent on complex neural networks are the most profoundly affected. These functions include speech, memory, learning, generation of ideas, and the planning of fine movements, especially those of the hands. In contrast, spontaneous emotional and hormonal responses appear relatively intact. Whereas failure to appreciate the physical limitations of the disease leads to frustration for therapist and client alike, a clear understanding of the better-preserved areas of competence offers avenues for real progress in learning, the building of satisfying relationships, and achievement of a quality of life.

scholarly journals KLF4 Induces Mesenchymal–Epithelial Transition (MET) by Suppressing Multiple EMT-Inducing Transcription Factors

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5135
Author(s):  
Ayalur Raghu Subbalakshmi ◽  
Sarthak Sahoo ◽  
Isabelle McMullen ◽  
Aaditya Narayan Saxena ◽  
Sudhanva Kalasapura Venugopal ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Patient Survival ◽  
Dynamic Processes ◽  
State Transitions ◽  
Specific Manner ◽  
Context Specific ◽  
Phenotypic Shift ◽  
Acting In Concert ◽  
Epithelial State ◽  
Mesenchymal Epithelial Transition

Epithelial–Mesenchymal Plasticity (EMP) refers to reversible dynamic processes where cells can transition from epithelial to mesenchymal (EMT) or from mesenchymal to epithelial (MET) phenotypes. Both these processes are modulated by multiple transcription factors acting in concert. While EMT-inducing transcription factors (TFs)—TWIST1/2, ZEB1/2, SNAIL1/2/3, GSC, and FOXC2—are well-characterized, the MET-inducing TFs are relatively poorly understood (OVOL1/2 and GRHL1/2). Here, using mechanism-based mathematical modeling, we show that transcription factor KLF4 can delay the onset of EMT by suppressing multiple EMT-TFs. Our simulations suggest that KLF4 overexpression can promote a phenotypic shift toward a more epithelial state, an observation suggested by the negative correlation of KLF4 with EMT-TFs and with transcriptomic-based EMT scoring metrics in cancer cell lines. We also show that the influence of KLF4 in modulating the EMT dynamics can be strengthened by its ability to inhibit cell-state transitions at the epigenetic level. Thus, KLF4 can inhibit EMT through multiple parallel paths and can act as a putative MET-TF. KLF4 associates with the patient survival metrics across multiple cancers in a context-specific manner, highlighting the complex association of EMP with patient survival.

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