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Full-Text Articles in Life Sciences

Gain-Of-Function Mutations In The Unc-2/Cav2alpha Channel Lead To Excitation-Dominant Synaptic Transmission In C. Elegans, Yung-Chi Huang, Jennifer K. Pirri, Diego Rayes, Shangbang Gao, Ben Mulcahy, Jeff Grant, Yasunori Saheki, Michael M. Francis, Mei Zhen, Mark J. Alkema Aug 2019

Gain-Of-Function Mutations In The Unc-2/Cav2alpha Channel Lead To Excitation-Dominant Synaptic Transmission In C. Elegans, Yung-Chi Huang, Jennifer K. Pirri, Diego Rayes, Shangbang Gao, Ben Mulcahy, Jeff Grant, Yasunori Saheki, Michael M. Francis, Mei Zhen, Mark J. Alkema

Neurobiology Publications and Presentations

Mutations in pre-synaptic voltage gated calcium channels can lead to familial hemiplegic migraine type 1 (FHM1). While mammalian studies indicate that the migraine brain is hyperexcitable due to enhanced excitation or reduced inhibition, the molecular and cellular mechanisms underlying this excitatory/inhibitory (E/I) imbalance are poorly understood. We identified a gain-of-function (gf) mutation in the Caenorhabditis elegans CaV2 channel alpha1 subunit, UNC-2, which leads to increased calcium currents. unc-2(zf35gf) mutants exhibit hyperactivity and seizure-like motor behaviors. Expression of the unc-2 gene with FHM1 substitutions R192Q and S218L leads to hyperactivity similar to that of unc-2(zf35gf) mutants. unc-2 ...


Differential Role Of Pontomedullary Glutamatergic Neuronal Populations In Sleep-Wake Control, Evelyn T. M. Erickson, Loris L. Ferrari, Heinrich S. Gompf, Christelle Anaclet Jul 2019

Differential Role Of Pontomedullary Glutamatergic Neuronal Populations In Sleep-Wake Control, Evelyn T. M. Erickson, Loris L. Ferrari, Heinrich S. Gompf, Christelle Anaclet

Neurobiology Publications and Presentations

Parafacial zone (PZ) GABAergic neurons play a major role in slow-wave-sleep (SWS), also called non-rapid eye movement (NREM) sleep. The PZ also contains glutamatergic neurons expressing the vesicular transporter for glutamate, isoform 2 (Vglut2). We hypothesized that PZ Vglut2-expressing (PZ(Vglut2)) neurons are also involved in sleep control, playing a synergistic role with PZ GABAergic neurons. To test this hypothesis, we specifically activated PZ(Vglut2) neurons using the excitatory chemogenetic receptor hM3Dq. Anatomical inspection of the injection sites revealed hM3Dq transfection in PZ, parabrachial nucleus (PB), sublaterodorsal nucleus (SLD) or various combinations of these three brain areas. Consistent with the ...


Co-Option Of Neurotransmitter Signaling For Inter-Organismal Communication In C. Elegans, Christopher D. Chute, Elizabeth M. Diloreto, Ying K. Zhang, Douglas K. Reilly, Diego Rayes, Veronica L. Coyle, Hee June Choi, Mark J. Alkema, Frank C. Schroeder, Jagan Srinivasan Jul 2019

Co-Option Of Neurotransmitter Signaling For Inter-Organismal Communication In C. Elegans, Christopher D. Chute, Elizabeth M. Diloreto, Ying K. Zhang, Douglas K. Reilly, Diego Rayes, Veronica L. Coyle, Hee June Choi, Mark J. Alkema, Frank C. Schroeder, Jagan Srinivasan

Neurobiology Publications and Presentations

Biogenic amine neurotransmitters play a central role in metazoan biology, and both their chemical structures and cognate receptors are evolutionarily conserved. Their primary roles are in cell-to-cell signaling, as biogenic amines are not normally recruited for communication between separate individuals. Here, we show that in the nematode C. elegans, a neurotransmitter-sensing G protein-coupled receptor, TYRA-2, is required for avoidance responses to osas#9, an ascaroside pheromone that incorporates the neurotransmitter, octopamine. Neuronal ablation, cell-specific genetic rescue, and calcium imaging show that tyra-2 expression in the nociceptive neuron, ASH, is necessary and sufficient to induce osas#9 avoidance. Ectopic expression in ...


Complement Targets Newborn Retinal Ganglion Cells For Phagocytic Elimination By Microglia, Sarah R. Anderson, Jianmin Zhang, Michael R. Steele, Cesar O. Romero, Amanda G. Kautzman, Dorothy P. Schafer, Monica L. Vetter Mar 2019

Complement Targets Newborn Retinal Ganglion Cells For Phagocytic Elimination By Microglia, Sarah R. Anderson, Jianmin Zhang, Michael R. Steele, Cesar O. Romero, Amanda G. Kautzman, Dorothy P. Schafer, Monica L. Vetter

Neurobiology Publications and Presentations

Microglia play important roles in shaping the developing CNS, and at early stages they have been proposed to regulate progenitor proliferation, differentiation, and neuronal survival. However, these studies reveal contradictory outcomes, highlighting the complexity of these cell-cell interactions. Here, we investigate microglia function during embryonic mouse retina development, where only microglia, progenitors, and neurons are present. In both sexes, we determine that microglia primarily interact with retinal neurons and find that depletion of microglia via conditional KO of the Csf1 receptor results in increased density of retinal ganglion cells (RGCs). Pharmacological inhibition of microglia also results in an increase in ...


Transforming Growth Factor-Beta Renders Ageing Microglia Inhibitory To Oligodendrocyte Generation By Cns Progenitors, Roey Baror, Bjorn Neumann, Michael Segel, Kevin J. Chalut, Stephen P.J. Fancy J, Dorothy P. Schafer, Robin J.M. Franklin Mar 2019

Transforming Growth Factor-Beta Renders Ageing Microglia Inhibitory To Oligodendrocyte Generation By Cns Progenitors, Roey Baror, Bjorn Neumann, Michael Segel, Kevin J. Chalut, Stephen P.J. Fancy J, Dorothy P. Schafer, Robin J.M. Franklin

Neurobiology Publications and Presentations

It is now well-established that the macrophage and microglial response to CNS demyelination influences remyelination by removing myelin debris and secreting a variety of signaling molecules that influence the behaviour of oligodendrocyte progenitor cells (OPCs). Previous studies have shown that changes in microglia contribute to the age-related decline in the efficiency of remyelination. In this study, we show that microglia increase their expression of the proteoglycan NG2 with age, and that this is associated with an altered micro-niche generated by aged, but not young, microglia that can divert the differentiation OPCs from oligodendrocytes into astrocytes in vitro. We further show ...