Cell-selective modulation of the Drosophila neuromuscular system by a neuropeptide

Neuropeptides can modulate physiological properties of neurons in a cell-specific manner. The present work examines whether a neuropeptide can also modulate muscle tissue in a cell-specific manner, using identified muscle cells in third instar larvae of fruit flies. DPKQDFMRFa, a modulatory peptide in the fruit fly Drosophila melanogaster, has been shown to enhance transmitter release from motor neurons and to elicit contractions by a direct effect on muscle cells. We report that DPKQDFMRFa causes a nifedipine-sensitive drop in input resistance in some muscle cells (6 and 7) but not others (12 and 13). The peptide also increased the amplitude of nerve-evoked contractions and compound excitatory junctional potentials (EJPs) to a greater degree in muscle cells 6 and 7 than 12 and 13. Knocking down FMRFa receptor (FR) expression separately in nerve and muscle indicate that both presynaptic and postsynaptic FR expression contributed to the enhanced contractions, but EJP enhancement was due mainly to presynaptic expression. Muscle-ablation showed that DPKQDFMRFa induced contractions and enhanced nerve-evoked contractions more strongly in muscle cells 6 and 7 than cells 12 and 13. In situ hybridization indicated that FR expression was significantly greater in muscle cells 6 and 7 than 12 and 13. Taken together, these results indicate that DPKQDFMRFa can elicit cell-selective effects on muscle fibres. The ability of neuropeptides to work in a cell-selective manner on neurons and muscle cells may help explain why so many peptides are encoded in invertebrate and vertebrate genomes

The action of octopamine on muscles of Drosophila melanogaster larvae

Octopamine (OA) and tyramine (TA) play important roles in homeostatic mechanisms, behavior, and modulation of neuromuscular junctions in arthropods. However, direct actions of these amines on muscle force production that are distinct from effects at the neuromuscular synapse have not been well studied. We utilize the technical benefits of the Drosophila larval preparation to distinguish the effects of OA and TA on the neuromuscular synapse from their effects on contractility of muscle cells. In contrast to the slight and often insignificant effects of TA, the action of OA was profound across all metrics assessed. We demonstrate that exogenous OA application decreases the input resistance of larval muscle fibers, increases the amplitude of excitatory junction potentials (EJPs), augments contraction force and duration, and at higher concentrations (10(-5) and 10(-4) M) affects muscle cells 12 and 13 more than muscle cells 6 and 7. Similarly, OA increases the force of synaptically driven contractions in a cell-specific manner. Moreover, such augmentation of contractile force persisted during direct muscle depolarization concurrent with synaptic block. OA elicited an even more profound effect on basal tonus. Application of 10(-5) M OA increased synaptically driven contractions by ≈ 1.1 mN but gave rise to a 28-mN increase in basal tonus in the absence of synaptic activation. Augmentation of basal tonus exceeded any physiological stimulation paradigm and can potentially be explained by changes in intramuscular protein mechanics. Thus we provide evidence for independent but complementary effects of OA on chemical synapses and muscle contractility

Prospective acceptability of digital phenotyping among pregnant and parenting people with opioid use disorder: A multisite qualitative study

BackgroundWhile medications for opioid use disorder (MOUD) effectively treat OUD during pregnancy and the postpartum period, poor treatment retention is common. Digital phenotyping, or passive sensing data captured from personal mobile devices, namely smartphones, provides an opportunity to understand behaviors, psychological states, and social influences contributing to perinatal MOUD non-retention. Given this novel area of investigation, we conducted a qualitative study to determine the acceptability of digital phenotyping among pregnant and parenting people with opioid use disorder (PPP-OUD).MethodsThis study was guided by the Theoretical Framework of Acceptability (TFA). Within a clinical trial testing a behavioral health intervention for PPP-OUD, we used purposeful criterion sampling to recruit 11 participants who delivered a child in the past 12  months and received OUD treatment during pregnancy or the postpartum period. Data were collected through phone interviews using a structured interview guide based on four TFA constructs (affective attitude, burden, ethicality, self-efficacy). We used framework analysis to code, chart, and identify key patterns within the data.ResultsParticipants generally expressed positive attitudes about digital phenotyping and high self-efficacy and low anticipated burden to participate in studies that collect smartphone-based passive sensing data. Nonetheless, concerns were noted related to data privacy/security and sharing location information. Differences in participant assessments of burden were related to length of time required and level of remuneration to participate in a study. Interviewees voiced broad support for participating in a digital phenotyping study with known/trusted individuals but expressed concerns about third-party data sharing and government monitoring.ConclusionDigital phenotyping methods were acceptable to PPP-OUD. Enhancements in acceptability include allowing participants to maintain control over which data are shared, limiting frequency of research contacts, aligning compensation with participant burden, and outlining data privacy/security protections on study materials

Metallic, magnetic and molecular nanocontacts

Scanning tunnelling microscopy and break-junction experiments realize metallic and molecular nanocontacts that act as ideal one-dimensional channels between macroscopic electrodes. Emergent nanoscale phenomena typical of these systems encompass structural, mechanical, electronic, transport, and magnetic properties. This Review focuses on the theoretical explanation of some of these properties obtained with the help of first-principles methods. By tracing parallel theoretical and experimental developments from the discovery of nanowire formation and conductance quantization in gold nanowires to recent observations of emergent magnetism and Kondo correlations, we exemplify the main concepts and ingredients needed to bring together ab initio calculations and physical observations. It can be anticipated that diode, sensor, spin-valve and spin-filter functionalities relevant for spintronics and molecular electronics applications will benefit from the physical understanding thus obtained

The control of load compensation in the hermit crab, Pagurus pollicarus: Characterization of a reflex discharge from postural motoneurons and its action in modulating force production

Oceanic hermit crabs occupy large gastropod shells. Shells are carried above, rather than dragged upon, the ocean floor during normal behavior. This is accomplished in part by the superficial muscles of the abdomen, which are activated in a tri-phasic pattern by local mechanoreceptors. Reflex activation of motoneurons consists of an initial burst, a period of inhibition, and a late discharge. ^ Results reported here indicate that this motor system acts in a feedforward fashion: (1) the reflex persists in the absence of peripheral feedback; (2) gain from change in afferent rate to change in reflex discharge is very small; (3) there is no relationship between the site of cuticular touch and the intensity or pattern of motoneuron activation; and (4) the reflex is generated by centrally located premotor neurons and does not require more than a single afferent potential (a trigger). ^ Although the tri-phasic reflex generates force in the postural muscle rapidly, this force rarely exceeds about 25% of maximum. Rate of force production is high early in the reflex, but the following decline in rate is comparable. We address the mechanisms underlying the transition from the first to second phase of motoneuron spiking and their contribution this change in force production. Two mechanisms are described: (1) the centrally generated ipsps of phase 2, and (2) a profound spike frequency adaptation (SFA) that is activated by phase 1 spiking that is voltage sensitive, and which is attenuated by transient repolarization of the membrane. ^ To address the question of whether tri-phasic motoneuron activation offers advantages over monophasic activation, variability in five parameters of reflex firing is assessed. Each of these parameters is correlated with neighboring reflex parameters and force production. Phase 3 frequency shows the greatest correlation with reflex force production. Phase 3 spike rate increases as a function of phase 2 duration and this is by means of SFA attenuation. Paradoxically, the relationship between phase 2 duration and force is weak. This cannot be explained by changes at the neuromuscular junction. We suggest that a non-linearity of force production, originating from intra-muscular dynamics, contributes to reflex force production.

Developmental expression of human tau in Drosophila melanogaster glial cells induces motor deficits and disrupts maintenance of PNS axonal integrity, without affecting synapse formation.

Tauopathies are a class of neurodegenerative diseases characterized by the abnormal phosphorylation and accumulation of the microtubule-associated protein, tau, in both neuronal and glial cells. Though tau pathology in glial cells is a prominent feature of many of these disorders, the pathological contribution of these lesions to tauopathy pathogenesis remains largely unknown. Moreover, while tau pathology is predominantly found in the central nervous system, a role for tau in the cells of the peripheral nervous system has been described, though not well characterized. To investigate the effects of glial tau expression on the development and maintenance of the peripheral nervous system, we utilized a Drosophila melanogaster model of tauopathy that expresses human wild-type tau in glial cells during development. We found that glial tau expression during development results in larval locomotor deficits and organismal lethality at the pupal stage, without affecting larval neuromuscular junction synapse development or post-synaptic amplitude. There was, however, a significant decrease in the decay time of synaptic potentials upon repeated stimulation of the motoneuron. Behavioral abnormalities were accompanied by glial cell death, disrupted maintenance of glial-axonal integrity, and the abnormal accumulation of the presynaptic protein, Bruchpilot, in peripheral nerve axons. Together, these data demonstrate that human tau expression in Drosophila glial cells does not affect neuromuscular junction synapse formation during development, but is deleterious to the maintenance of glial-axonal interactions in the peripheral nervous system