The Neural and Molecular Mechanisms Regulating Male Locomotion during Caenorhabditis elegans Mating Behavior

In key survival behaviors like predator-prey interactions and mating, animals have to integrate dynamic sensory inputs from a moving target and regulate their motor outputs on moment-to-moment basis. The molecular underpinnings of such goal-oriented behaviors are not well understood because of the genomic and neural system complexities of many animals. Here I take advantage of the anatomical simplicity of the nematode worm Caenorhabditis elegans and its amenability to optogenetics to interrogate the neural mechanisms underlying male mating behavior. Male mating is a goal oriented behavioral sequence and serves as a useful paradigm for exploring neural control of sex-specific behaviors, behavioral sequence execution and decision-making. When not engaged in mating the male, like the hermaphrodite, explores his environment with predominantly forward locomotion. However, when the male contacts a potential mate he immediately places his tail against her surface and searches for the vulva, moving backwards. Male-specific sensory rays of the tail are responsible for sensing mate contact, inducing tail apposition and backward movement. Using a combination of cell-specific laser ablation, optogentics and mutant analyses, I show that the male exploits the sex-shared locomotory system to control his mating movement. The rays exert their affect by acting through at least two downstream pathways. One pathway is defined by male-specific interneurons PVY and PVX which activate backward command interneurons AVA(L/R) and shift the directional bias to backward. This AVA activation is mediated by cholinergic receptor subunits ACR-18, ACR-16 and UNC-29, which is an atypical mode for command interneuron regulation. The second pathway is defined by male-specific interneurons EF1-3. EFs may promote backing by inhibiting sex-shared AVB(L/R) forward command interneurons. Upon vulva detection by the hook sensilla, locomotion ceases by the redundant action of hook neurons HOA and HOB. Surprisingly, PVY/PVX and EFs activity is required for holding the tail at the vulva. Taken together these data suggest that a distributed processing strategy underlies male’s accurate, rapid and robust movement control during mating. The male-specific nature of his behavior is due male-specific control of sex-shared circuitry. Conceivably, similar design and processing strategies may underlie the circuitry controlling analogous behaviors in more complex nervous systems

Next-Generation Solid-State Quantum Emitters

This thesis details two types of deterministic solid-state quantum emitters, an optically-driven quantum dot source in a tapered nanowire waveguide, and an electrically-driven source implemented by integrating a single-electron pump into a two-dimensional p-n junction. A finite-difference time-domain model of the optically-driven nanowire quantum dot source yielded optimized architectural parameters required to obtain a high transmission efficiency and a Gaussian far-field emission profile. An additional model of an electrically-gated nanowire source examined the effect of the surrounding structures on the emission properties of the source. A successfully working prototype p-n junction device as a precursor to the electrically-driven quantum emitter was implemented by simultaneously inducing positive and negative two-dimensional carrier gases in an undoped semiconductor heterostructure. This device, fabricated in-house, offers a path forward in the development of a new class of bright, deterministic sources of single- and entangled-photons

Multiple doublesex-Related Genes Specify Critical Cell Fates in a C. elegans Male Neural Circuit

In most animal species, males and females exhibit differences in behavior and morphology that relate to their respective roles in reproduction. DM (Doublesex/MAB-3) domain transcription factors are phylogenetically conserved regulators of sexual development. They are thought to establish sexual traits by sex-specifically modifying the activity of general developmental programs. However, there are few examples where the details of these interactions are known, particularly in the nervous system.In this study, we show that two C. elegans DM domain genes, dmd-3 and mab-23, regulate sensory and muscle cell development in a male neural circuit required for mating. Using genetic approaches, we show that in the circuit sensory neurons, dmd-3 and mab-23 establish the correct pattern of dopaminergic (DA) and cholinergic (ACh) fate. We find that the ETS-domain transcription factor gene ast-1, a non-sex-specific, phylogenetically conserved activator of dopamine biosynthesis gene transcription, is broadly expressed in the circuit sensory neuron population. However, dmd-3 and mab-23 repress its activity in most cells, promoting ACh fate instead. A subset of neurons, preferentially exposed to a TGF-beta ligand, escape this repression because signal transduction pathway activity in these cells blocks dmd-3/mab-23 function, allowing DA fate to be established. Through optogenetic and pharmacological approaches, we show that the sensory and muscle cell characteristics controlled by dmd-3 and mab-23 are crucial for circuit function.In the C. elegans male, DM domain genes dmd-3 and mab-23 regulate expression of cell sub-type characteristics that are critical for mating success. In particular, these factors limit the number of DA neurons in the male nervous system by sex-specifically regulating a phylogenetically conserved dopamine biosynthesis gene transcription factor. Homologous interactions between vertebrate counterparts could regulate sex differences in neuron sub-type populations in the brain

Stable electroluminescence in ambipolar dopant-free lateral p-n junctions

Dopant-free lateral p-n junctions in the GaAs/AlGaAs material system have attracted interest due to their potential use in quantum optoelectronics (e.g., optical quantum computers or quantum repeaters) and ease of integration with other components, such as single electron pumps and spin qubits. A major obstacle to integration has been unwanted charge accumulation at the p-n junction gap that suppresses light emission, either due to enhanced non-radiative recombination or inhibition of p-n current. Typically, samples must frequently be warmed to room temperature to dissipate this built-up charge and restore light emission in a subsequent cooldown. Here, we introduce a practical gate voltage protocol that clears this parasitic charge accumulation, in-situ at low temperature, enabling the indefinite cryogenic operation of devices. This reset protocol enabled the optical characterization of stable, bright, dopant-free lateral p-n junctions with electroluminescence linewidths among the narrowest (< 1 meV; < 0.5 nm) reported in this type of device. It also enabled the unambiguous identification of the ground state of neutral free excitons (heavy and light holes), as well as charged excitons (trions). The free exciton emission energies for both photoluminescence and electroluminescence are found to be nearly identical (within 0.2 meV or 0.1 nm). The binding and dissociation energies for free and charged excitons are reported. A free exciton lifetime of 237 ps was measured by time-resolved electroluminescence, compared to 419 ps with time-resolved photoluminescence.Comment: Main text: 5 pages and 5 figures. Supplementary: 18 pages and 11 figure

Drug-Dependent Behaviors and Nicotinic Acetylcholine Receptor Expressions in Caenorhabditis elegans Following Chronic Nicotine Exposure

Nicotine, the major psychoactive compound in tobacco, targets nicotinic acetylcholine receptors (nAChRs) and results in drug dependence. The nematode Caenorhabditis elegans’ (C. elegans) genome encodes conserved and extensive nicotinic receptor subunits, representing a useful system to investigate nicotine-induced nAChR expressions in the context of drug dependence. However, the in vivo expression pattern of nAChR genes under chronic nicotine exposure has not been fully investigated. To define the role of nAChR genes involved in nicotine-induced locomotion changes and the development of tolerance to these effects, we characterized the locomotion behavior combining the use of two systems: the Worm Tracker hardware and the WormLab software. Our results indicate that the combined system is an advantageous alternative to define drug-dependent locomotion behavior in C. elegans. Chronic (24-hour dosing) nicotine exposure at 6.17 and 61.7 μM induced nicotine-dependent behaviors, including drug stimulation, tolerance/adaption, and withdrawal responses. Specifically, the movement speed of naïve worms on nicotine-containing environments was significantly higher than on nicotine-free environments, suggesting locomotion stimulation by nicotine. In contrast, the 24-hour 6.17 μM nicotine-treated worms exhibited significantly higher speeds on nicotine-free plates than on nicotine-containing plates. Furthermore significantly increased locomotion behavior during nicotine cessation was observed in worms treated with a higher nicotine concentration of 61.7 μM. The relatively low locomotion speed of nicotine-treated worms on nicotine-containing environments also indicates adaption/tolerance of worms to nicotine following chronic nicotine exposure. In addition, this study provides useful information regarding the comprehensive in vivo expression profile of the 28 “core” nAChRs following different dosages of chronic nicotine treatments. Eleven genes (lev-1, acr-6, acr-7, acr-11, lev-8, acr-14, acr-16, acr-20, acr-21, ric-3, and unc-29) were significantly up-regulated following 61.7 μM nicotine treatment, in which worms showed significantly increased locomotion behavior. This study provides insights into the linkage between nicotine-induced locomotion behavior and the regulation of nicotinic acetylcholine receptors

A cellular and regulatory map of the cholinergic nervous system of C. elegans

Nervous system maps are of critical importance for understanding how nervous systems develop and function. We systematically map here all cholinergic neuron types in the male and hermaphrodite C. elegans nervous system. We find that acetylcholine (ACh) is the most broadly used neurotransmitter and we analyze its usage relative to other neurotransmitters within the context of the entire connectome and within specific network motifs embedded in the connectome. We reveal several dynamic aspects of cholinergic neurotransmitter identity, including a sexually dimorphic glutamatergic to cholinergic neurotransmitter switch in a sex-shared interneuron. An expression pattern analysis of ACh-gated anion channels furthermore suggests that ACh may also operate very broadly as an inhibitory neurotransmitter. As a first application of this comprehensive neurotransmitter map, we identify transcriptional regulatory mechanisms that control cholinergic neurotransmitter identity and cholinergic circuit assembly. DOI: http://dx.doi.org/10.7554/eLife.12432.00