inhibits TIR-1/SARM1 induced axon degeneration.

Emerging evidence suggests the microbiome critically influences the onset and progression of neurodegenerative diseases; however, the identity of neuroprotective bacteria and the molecular mechanisms that respond within the host remain largely unknown. We took advantage of well characterized nervous system and ability to eat uni-bacterial diets to determine how metabolites and neuroprotective molecules from single species of bacteria suppress degeneration of motor neurons. We found significantly protects against degeneration induced by overexpressing a key regulator of axon degeneration, TIR-1/SARM1.

Vitamin B produced by gut bacteria modulates cholinergic signalling.

A growing body of evidence indicates that gut microbiota influence brain function and behaviour. However, the molecular basis of how gut bacteria modulate host nervous system function is largely unknown. Here we show that vitamin B-producing bacteria that colonize the intestine can modulate excitatory cholinergic signalling and behaviour in the host Caenorhabditis elegans.

PARP knockdown promotes synapse reformation after axon injury.

Injured nervous systems are often incapable of self-repairing, resulting in permanent loss of function and disability. To restore function, a severed axon must not only regenerate, but must also reform synapses with target cells. Together, these processes beget functional axon regeneration.

Cannabinoids activate the insulin pathway to modulate mobilization of cholesterol in C. elegans.

The nematode Caenorhabditis elegans requires exogenous cholesterol to survive and its depletion leads to early developmental arrest. Thus, tight regulation of cholesterol storage and distribution within the organism is critical. Previously, we demonstrated that the endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG) plays a key role in C.

Age-associated changes to neuronal dynamics involve a disruption of excitatory/inhibitory balance in .

In the aging brain, many of the alterations underlying cognitive and behavioral decline remain opaque. offers a powerful model for aging research, with a simple, well-studied nervous system to further our understanding of the cellular modifications and functional alterations accompanying senescence. We perform multi-neuronal functional imaging across the aged nervous system, measuring an age-associated breakdown in system-wide functional organization.

Co-transmission of neuropeptides and monoamines choreograph the C. elegans escape response.

Co-localization and co-transmission of neurotransmitters and neuropeptides is a core property of neural signaling across species. While co-transmission can increase the flexibility of cellular communication, understanding the functional impact on neural dynamics and behavior remains a major challenge. Here we examine the role of neuropeptide/monoamine co-transmission in the orchestration of the C.

A conserved neuropeptide system links head and body motor circuits to enable adaptive behavior.

Neuromodulators promote adaptive behaviors that are often complex and involve concerted activity changes across circuits that are often not physically connected. It is not well understood how neuromodulatory systems accomplish these tasks. Here, we show that the NLP-12 neuropeptide system shapes responses to food availability by modulating the activity of head and body wall motor neurons through alternate G-protein coupled receptor (GPCR) targets, CKR-1 and CKR-2.

Distinct neuropeptide-receptor modules regulate a sex-specific behavioral response to a pheromone.

Dioecious species are a hallmark of the animal kingdom, with opposing sexes responding differently to identical sensory cues. Here, we study the response of C. elegans to the small-molecule pheromone, ascr#8, which elicits opposing behavioral valences in each sex.

The transcription factor LAG-1/CSL plays a Notch-independent role in controlling terminal differentiation, fate maintenance, and plasticity of serotonergic chemosensory neurons.

During development, signal-regulated transcription factors (TFs) act as basal repressors and upon signalling through morphogens or cell-to-cell signalling shift to activators, mediating precise and transient responses. Conversely, at the final steps of neuron specification, terminal selector TFs directly initiate and maintain neuron-type specific gene expression through enduring functions as activators. C.

Corollary discharge promotes a sustained motor state in a neural circuit for navigation.

Animals exhibit behavioral and neural responses that persist on longer timescales than transient or fluctuating stimulus inputs. Here, we report that uses feedback from the motor circuit to a sensory processing interneuron to sustain its motor state during thermotactic navigation. By imaging circuit activity in behaving animals, we show that a principal postsynaptic partner of the AFD thermosensory neuron, the AIY interneuron, encodes both temperature and motor state information.

Flexible motor sequence generation during stereotyped escape responses.

Complex animal behaviors arise from a flexible combination of stereotyped motor primitives. Here we use the escape responses of the nematode to study how a nervous system dynamically explores the action space. The initiation of the escape responses is predictable: the animal moves away from a potential threat, a mechanical or thermal stimulus.

HIF-1 Has a Central Role in Organismal Response to Selenium.

Selenium is a trace element for most organisms; its deficiency and excess are detrimental. Selenium beneficial effects are mainly due to the role of the 21 genetically encoded amino acid selenocysteine (Sec). Selenium also exerts Sec-independent beneficial effects.

The flight response impairs cytoprotective mechanisms by activating the insulin pathway.

An animal's stress response requires different adaptive strategies depending on the nature and duration of the stressor. Whereas acute stressors, such as predation, induce a rapid and energy-demanding fight-or-flight response, long-term environmental stressors induce the gradual and long-lasting activation of highly conserved cytoprotective processes. In animals across the evolutionary spectrum, continued activation of the fight-or-flight response weakens the animal's resistance to environmental challenges.

Gain-of-function mutations in the UNC-2/CaV2α channel lead to excitation-dominant synaptic transmission in .

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 CaV2 channel α1 subunit, UNC-2, which leads to increased calcium currents.

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 cell-to-cell signaling, as biogenic amines are not normally recruited for communication between separate individuals. Here, we show that in the nematode C.

Diapause induces functional axonal regeneration after necrotic insult in C. elegans.

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.

Neurexin directs partner-specific synaptic connectivity in .

In neural circuits, individual neurons often make projections onto multiple postsynaptic partners. Here, we investigate molecular mechanisms by which these divergent connections are generated, using dyadic synapses in as a model. We report that /neurexin directs divergent connectivity through differential actions at synapses with partnering neurons and muscles.

The Genetic Basis of Natural Variation in Caenorhabditis elegans Telomere Length.

Telomeres are involved in the maintenance of chromosomes and the prevention of genome instability. Despite this central importance, significant variation in telomere length has been observed in a variety of organisms. The genetic determinants of telomere-length variation and their effects on organismal fitness are largely unexplored.

Imprinting: When Early Life Memories Make Food Smell Bad.

A recent study has found that pathogen exposure early in the life of the nematode Caenorhabditis elegans leads to a long-lasting aversion that requires distinct sets of neurons for the formation and retrieval of the imprinted memory.

Caenorhabditis elegans exhibit a coupling between the defecation motor program and directed locomotion.

Distinct motor programs can be coupled to refine the repertoire of behavior dynamics. However, mechanisms underlying such coupling are poorly understood. The defecation motor program (DMP) of C.

A Change in the Ion Selectivity of Ligand-Gated Ion Channels Provides a Mechanism to Switch Behavior.

Behavioral output of neural networks depends on a delicate balance between excitatory and inhibitory synaptic connections. However, it is not known whether network formation and stability is constrained by the sign of synaptic connections between neurons within the network. Here we show that switching the sign of a synapse within a neural circuit can reverse the behavioral output.

Illuminating neural circuits and behaviour in Caenorhabditis elegans with optogenetics.

The development of optogenetics, a family of methods for using light to control neural activity via light-sensitive proteins, has provided a powerful new set of tools for neurobiology. These techniques have been particularly fruitful for dissecting neural circuits and behaviour in the compact and transparent roundworm Caenorhabditis elegans. Researchers have used optogenetic reagents to manipulate numerous excitable cell types in the worm, from sensory neurons, to interneurons, to motor neurons and muscles.

Presynaptic BK channel localization is dependent on the hierarchical organization of alpha-catulin and dystrobrevin and fine-tuned by CaV2 calcium channels.

Background: Large conductance, calcium-activated BK channels regulate many important physiological processes, including smooth muscle excitation, hormone release and synaptic transmission. The biological roles of these channels hinge on their unique ability to respond synergistically to both voltage and cytosolic calcium elevations. Because calcium influx is meticulously regulated both spatially and temporally, the localization of BK channels near calcium channels is critical for their proper function.