Voltage-induced calcium release in body muscles.

Type 1 voltage-activated calcium channels (CaV1) in the plasma membrane trigger calcium release from the sarcoplasmic reticulum (SR) by two mechanisms. In voltage-induced calcium release (VICR), CaV1 voltage sensing domains are directly coupled to ryanodine receptors (RYRs), an SR calcium channel. In calcium-induced calcium release (CICR), calcium ions flowing through activated CaV1 channels bind and activate RYR channels.

Stereotyped behavioral maturation and rhythmic quiescence in embryos.

Systematic analysis of rich behavioral recordings is being used to uncover how circuits encode complex behaviors. Here, we apply this approach to embryos. What are the first embryonic behaviors and how do they evolve as early neurodevelopment ensues? To address these questions, we present a systematic description of behavioral maturation for embryos.

Shank promotes action potential repolarization by recruiting BK channels to calcium microdomains.

Mutations altering the scaffolding protein Shank are linked to several psychiatric disorders, and to synaptic and behavioral defects in mice. Among its many binding partners, Shank directly binds CaV1 voltage activated calcium channels. Here, we show that the SHN-1/Shank promotes CaV1 coupling to calcium activated potassium channels.

EFHC1, implicated in juvenile myoclonic epilepsy, functions at the cilium and synapse to modulate dopamine signaling.

Neurons throughout the mammalian brain possess non-motile cilia, organelles with varied functions in sensory physiology and cellular signaling. Yet, the roles of cilia in these neurons are poorly understood. To shed light into their functions, we studied EFHC1, an evolutionarily conserved protein required for motile cilia function and linked to a common form of inherited epilepsy in humans, juvenile myoclonic epilepsy (JME).

Insights into the roles of CMK-1 and OGT-1 in interstimulus interval-dependent habituation in .

Habituation is a ubiquitous form of non-associative learning observed as a decrement in responding to repeated stimulation that cannot be explained by sensory adaptation or motor fatigue. One of the defining characteristics of habituation is its sensitivity to the rate at which training stimuli are presented-animals habituate faster in response to more rapid stimulation. The molecular mechanisms underlying this interstimulus interval (ISI)-dependent characteristic of habituation remain unknown.

High-Throughput Analysis of Behavior Under the Control of Optogenetics in Caenorhabditis elegans.

In this unit, we describe an inexpensive and versatile method for optogenetic stimulation of a large population of genetically engineered Caenorhabditis elegans worms while quantitatively analyzing behavior. A custom light-emitting diode light source is used to deliver blue-light stimuli, causing direct depolarization of neurons expressing the light-gated cation channel Channelrhodopsin-2, which in turn evokes behavioral responses. The behavioral responses are recorded by a high-throughput machine vision-based tracking system, the Multi-Worm Tracker, for detailed analysis.

An Afferent Neuropeptide System Transmits Mechanosensory Signals Triggering Sensitization and Arousal in C. elegans.

Sensitization is a simple form of behavioral plasticity by which an initial stimulus, often signaling danger, leads to increased responsiveness to subsequent stimuli. Cross-modal sensitization is an important feature of arousal in many organisms, yet its molecular and neural mechanisms are incompletely understood. Here we show that in C.

Reflective imaging improves spatiotemporal resolution and collection efficiency in light sheet microscopy.

Light-sheet fluorescence microscopy (LSFM) enables high-speed, high-resolution, and gentle imaging of live specimens over extended periods. Here we describe a technique that improves the spatiotemporal resolution and collection efficiency of LSFM without modifying the underlying microscope. By imaging samples on reflective coverslips, we enable simultaneous collection of four complementary views in 250 ms, doubling speed and improving information content relative to symmetric dual-view LSFM.

Habituation as an adaptive shift in response strategy mediated by neuropeptides.

Habituation is a non-associative form of learning characterized by a decremented response to repeated stimulation. It is typically framed as a process of selective attention, allowing animals to ignore irrelevant stimuli in order to free up limited cognitive resources. However, habituation can also occur to threatening and toxic stimuli, suggesting that habituation may serve other functions.

Visualizing Calcium Flux in Freely Moving Nematode Embryos.

The lack of physiological recordings from Caenorhabditis elegans embryos stands in stark contrast to the comprehensive anatomical and gene expression datasets already available. Using light-sheet fluorescence microscopy to address the challenges associated with functional imaging at this developmental stage, we recorded calcium dynamics in muscles and neurons and developed analysis strategies to relate activity and movement. In muscles, we found that the initiation of twitching was associated with a spreading calcium wave in a dorsal muscle bundle.

Dopamine receptor DOP-4 modulates habituation to repetitive photoactivation of a C. elegans polymodal nociceptor.

Habituation is a highly conserved phenomenon that remains poorly understood at the molecular level. Invertebrate model systems, like Caenorhabditis elegans, can be a powerful tool for investigating this fundamental process. Here we established a high-throughput learning assay that used real-time computer vision software for behavioral tracking and optogenetics for stimulation of the C.

Accumulation of Laminin Monomers in Drosophila Glia Leads to Glial Endoplasmic Reticulum Stress and Disrupted Larval Locomotion.

Unlabelled: The nervous system is surrounded by an extracellular matrix composed of large glycoproteins, including perlecan, collagens, and laminins. Glial cells in many organisms secrete laminin, a large heterotrimeric protein consisting of an α, β, and γ subunit. Prior studies have found that loss of laminin subunits from vertebrate Schwann cells causes loss of myelination and neuropathies, results attributed to loss of laminin-receptor signaling.

Casting a genome-wide net for learning mutants.

Wolman et al. (2015) report a forward genetic screen in zebrafish that implicated pregnancy-associated plasma protein-aa in habituation of the acoustic startle response. PAPP-AA is expressed in the underlying circuit, including Mauthner cells, and regulates habituation via IGF signaling.

Mechanisms of plasticity in a Caenorhabditis elegans mechanosensory circuit.

Despite having a small nervous system (302 neurons) and relatively short lifespan (14-21 days), the nematode Caenorhabditis elegans has a substantial ability to change its behavior in response to experience. The behavior discussed here is the tap withdrawal response, whereby the worm crawls backwards a brief distance in response to a non-localized mechanosensory stimulus from a tap to the side of the Petri plate within which it lives. The neural circuit that underlies this behavior is primarily made up of five sensory neurons and four pairs of interneurons.

Intensity discrimination deficits cause habituation changes in middle-aged Caenorhabditis elegans.

The ability to learn and remember is critical for all animals to survive in the ever-changing environment. As we age, many of our biological faculties decay and of these, decline in learning and memory can be the most distressing. To carefully define age-dependent changes in learning during reproductive age in the nematode Caenorhabditis elegans, we performed a parametric behavioral study of habituation to nonlocalized mechanical stimuli (petri plate taps) over a range of intensities in middle-aged worms.

Some like it hot: decoding neurotransmission in the worm's thermotaxis circuit.

EMBO J 30 7, 1376–1388 (2011); published online February 08 2011 neuroscientists are on track to describe the world's first functional connectome. The work by Ohnishi et al (2011) is an excellent example of this effort. Characterizing glutamatergic transmission within the neural circuit controlling locomotion in thermal gradients, they found that two thermosensory neurons, AFD and AWC, transmitted glutamate signals of opposite polarity to downstream interneuron AIY.

The importance of touch in development.

Developmental delay is common in children deprived of normal sensory stimulation - for example, in premature neonates and some institutionalized children. Touch has emerged as an important modality for the facilitation of growth and development; positive effects of supplemental mechanosensory stimulation have been demonstrated in a wide range of organisms, from worm larvae to rat pups to human infants. Animal models are being used to elucidate the cellular and molecular mechanisms underlying these effects.

An elegant mind: learning and memory in Caenorhabditis elegans.

This article reviews the literature on learning and memory in the soil-dwelling nematode Caenorhabditis elegans. Paradigms include nonassociative learning, associative learning, and imprinting, as worms have been shown to habituate to mechanical and chemical stimuli, as well as learn the smells, tastes, temperatures, and oxygen levels that predict aversive chemicals or the presence or absence of food. In each case, the neural circuit underlying the behavior has been at least partially described, and forward and reverse genetics are being used to elucidate the underlying cellular and molecular mechanisms.

C. elegans: social interactions in a "nonsocial" animal.

As self-fertilizing nematodes, Caenorhabditis elegans do not normally come to mind when one thinks of social animals. However, their reproductive mode is optimized for rapid population growth, and although they do not form structured societies, conspecifics are an important source of sensory input. A pheromone signal underlies multiple complex behaviors, including diapause, male-mating, and aggregation.

Behavioral Plasticity in the C. elegans Mechanosensory Circuit.

This review outlines research into the cellular and molecular mechanisms underlying a simple behavior in the soil-dwelling nematode, C. elegans. A tap administered to the side of a petri plate acts as a nonlocalized mechanical stimulus to the worms within.