Biology subjects

Alkema, M.

Publications and source records attributed to Alkema, M..

3 recordsLinked to original sources

bioRxiv2018

Acute-stress impairs cytoprotective mechanisms through neural inhibition of the insulin pathway

Persistent activation of the \"fight-or-flight\" response accelerates aging and increases the susceptibility to disease. We show that repeated induction of the C. elegans flight response inhibits conserved cytoprotective mechanisms. This acute-stress response activates neurons that release tyramine, the invertebrate analog of adrenaline/noradrenaline. Tyramine stimulates the DAF-2/Insulin/IGF-1 pathway and precludes the nuclear translocation of the DAF-16/FOXO transcription factor through the activation of an adrenergic-like receptor TYRA-3 in the intestine. In contrast, environmental long-term stressors, such as heat or oxidative stress, reduce tyramine release allowing the induction of FOXO-dependent cytoprotective genes. These findings demonstrate how a neural stress-hormone signaling provides a state-dependent neural switch between acute and long-term stress responses, and provide mechanistic insights how acute stress impairs cellular defensive systems.\n\nOne Sentence Summary: The \"fight-or-flight\" response reduces resistance to environmental challenges.

neuroscience↗

bioRxiv2018

Co-option of neurotransmitter signaling for inter-organismal communication in C. elegans

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 intra-organismal signaling, whereas biogenic amines are not normally recruited for communication between separate individuals. Here, we show that in 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 the AWA neuron, which is generally associated with attractive responses, reverses the response to osas#9, resulting in attraction instead of avoidance behavior, confirming that TYRA-2 partakes in sensing osas#9. The TYRA-2/osas#9 signaling system thus represents an inter-organismal communication channel that evolved via co-option of a neurotransmitter and its cognate receptor.

neuroscience↗

bioRxiv2017

Excitatory Motor Neurons Function As Central Pattern Generators In An Anatomically Compressed Motor Circuit For Reverse Locomotion

Central pattern generators are cell- or network-driven oscillators that underlie motor rhythmicity. The existence and identity of C. elegans CPGs are unknown. Through cell ablation, electrophysiology, and calcium imaging, we identified oscillators for C. elegans reverse locomotion. We show that the cholinergic and excitatory class A motor neurons exhibit intrinsic and oscillatory activity, and such an activity can drive reverse locomotion without premotor interneurons. Regulation of their oscillatory activity, either through effecting the P/Q/N high voltage-activated calcium channel, an endogenous constituent of their intrinsic oscillation, or, via the dual regulation by descending premotor interneurons, determines the propensity, velocity, and sustention of reverse locomotion. Thus, the reversal motor neuron themselves serve as distributed local oscillators; regulation of their intrinsic activity controls the reversal motor state. These findings exemplify anatomic and functional compression: motor executors integrate the role of rhythm generation in a locomotor network that is constrained by small cell numbers.\n\nHighlightsO_LIThe class A motor neurons (A-MNs) intrinsically oscillate.\nC_LIO_LIHigh voltage-activated calcium channel is a constituent of A-MN oscillation.\nC_LIO_LIRegulation of A-MN oscillation by interneurons determines the reversal state.\nC_LIO_LIA-MNs integrate the role of multiple neuron types in large locomotor networks.\nC_LI

neuroscience↗