Neural control of Caenorhabditis elegans forward locomotion: the role of sensory feedback

This paper presents a simple yet biologically-grounded model for the neural control of Caenorhabditis elegans forward locomotion. We identify a minimal circuit within the C. elegans ventral cord that is likely to be sufficient to generate and sustain forward locomotion in vivo. This limited subcircuit appears to contain no obvious central pattern generated control. For that subcircuit, we present a model that relies on a chain of oscillators along the body which are driven by local and proximate mechano-sensory input. Computer simulations were used to study the model under a variety of conditions and to test whether it is behaviourally plausible. Within our model, we find that a minimal circuit of AVB interneurons and B-class motoneurons is sufficient to generate and sustain fictive forward locomotion patterns that are robust to significant environmental perturbations. The model predicts speed and amplitude modulation by the AVB command interneurons. An extended model including D-class motoneurons is included for comparison. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. John Bryden and Netta Cohen contributed equally to this work.     

The role of auditory feedback in vocal learning and maintenance

Auditory experience is critical for the acquisition and maintenance of learned vocalizations in both humans and songbirds. Despite the central role of auditory feedback in vocal learning and maintenance, where and how auditory feedback affects neural circuits important to vocal control remain poorly understood. Recent studies of singing birds have uncovered neural mechanisms by which feedback perturbations affect vocal plasticity and also have identified feedback-sensitive neurons at or near sites of auditory and vocal motor interaction. Additionally, recent studies in marmosets have underscored that even in the absence of vocal learning, vocalization remains flexible in the face of changing acoustical environments, pointing to rapid interactions between auditory and vocal motor systems. Finally, recent studies show that a juvenile songbird's initial auditory experience of a song model has long-lasting effects on sensorimotor neurons important to vocalization, shedding light on how auditory memories and feedback interact to guide vocal learning.     

The central projections of mesothoracic sensory neurons in wild-type Drosophila and bithorax mutants

Sensory axons entering the CNS from large campaniform sensilla on the normal, mesothoracic wings of four-winged flies of the genotype $\text{bx}{}^3\text{pbx}\text{Ubx}{}^{130}$ follow the same two tracts as do the corresponding axons in wild-type flies. However, they produce more branches along the ventromedial tract (including some in the mesothoracic neuromere), more fibers crossing the midline in the metathorax, and several other modifications of the wild-type pattern. No morphological differences between the receptors in normal and mutant flies could be detected, even with the SEM. The extra branching and other altered characteristics are present in bithorax flies which are also genetically wingless and do not form the homeotic appendages, so they appear to be due to the $\text{bx}{}^3\text{pbx}\text{Ubx}{}^{130}$ or $\text{bx}{}^3\text{Ubx}{}^{130}$ genotype and not to some effect of the axons from the homeotic wings.     

Reflexes and preflexes: on the role of sensory feedback on rhythmic patterns in insect locomotion

Neuromuscular systems are stabilized and controlled by both feedforward and feedback signals. Feedforward pathways driven by central pattern generators (CPGs), in conjunction with preflexive mechanical reaction forces and nonlinear muscle properties, can produce stable stereotypical gaits. Feedback is nonetheless present in both slow and rapid running, and preflexive mechanisms can join with neural reflexes originating in proprioceptive sensors to yield robust behavior in uncertain environments. Here, we develop a single degree-of-freedom neuromechanical model representing a joint actuated by an agonist/antagonist muscle pair driven by motoneurons and a CPG in a periodic rhythm characteristic of locomotion. We consider two characteristic feedback modes: phasic and tonic. The former encodes states such as position in the timing of individual spikes, while the latter can transmit graded measures of force and other continuous variables as spike rates. We use results from phase reduction and averaging theory to predict phase relationships between CPG and motoneurons in the presence of feedback and compare them with simulations of the neuromechanical model, showing that both phasic and tonic feedback can shift motoneuronal timing and thereby affect joint motions. We find that phase changes in neural activation can cooperate with preflexive displacement and velocity effects on muscle force to compensate for externally applied forces, and that these effects qualitatively match experimental observations in the cockroach.     

The role of feedback during singing and flight in Drosophila melanogaster

ABSTRACT. During Drosophila courtship 'pulse song', muscle potentials occur at two points during the cycle of neuromuscular events which result in a sound pulse being produced. The dorsal longitudinal, second and third dorsal ventral and axillary muscles show potentials 18 ms before each sound pulse while the first dorsal ventral, basalar and sternobasalar muscles fire 3 ms after the onset of each pulse. The timing of these events remains unaltered in animals with the antennae removed, indicating that acoustic feedback is not an important factor. Courting vestigial flies, in the absence of detectable wing base movements, produce indirect muscle potentials at the appropriate song inter-pulse intervals. Thus proprioceptive feedback is also unimportant in determining the intervals between pulses. During putative 'sine song', 'pulse song' and flight in vestigial flies, however, the timing of basalar muscle potentials is abnormal. Also, if the wing is driven externally at a frequency different from that of normal flight, basalar and, to a lesser extent, first dorsal ventral muscles, are phase locked to the driving frequency. These two results suggest that the timing of those muscles which fire at the beginning of the sound pulses is set by proprioceptive feedback. A model of song production is proposed which takes into account the data from this and from previously published papers.     

IFT52 plays an essential role in sensory cilia formation and neuronal sensory function in Drosophila

Cilia are microtubule-based, hair-like organelles involved in sensory function or motility, playing critical roles in many physiological processes such as reproduction, organ development, and sensory perception. In insects, cilia are restricted to certain sensory neurons and sperms, being important for chemical and mechanical sensing, and fertility. Although great progress has been made regarding the mechanism of cilia assembly, the formation of insect cilia remains poorly understand, even in the insect model organism Drosophila. Intraflagellar transport (IFT) is a cilia-specific complex that traffics protein cargos bidirectionally along the ciliary axoneme and is essential for most cilia. Here we investigated the role of IFT52, a core component of IFT-B, in cilia/flagellar formation in Drosophila. We show that Drosophila IFT52 is distributed along the sensory neuronal cilia, and is essential for sensory cilia formation. Deletion of Ift52 results in severe defects in cilia-related sensory behaviors. It should be noted that IFT52 is not detected in spermatocyte cilia or sperm flagella of Drosophila. Accordingly, ift52 mutants can produce sperms with normal motility, supporting a dispensable role of IFT in Drosophila sperm flagella formation. Altogether, IFT52 is a conserved protein essential for sensory cilia formation and sensory neuronal function in insects.     

The role of cercal sensory feedback during spermatophore transfer in the cricket, Acheta domesticus

The role of the cerci in the spermatophore transfer behavior of the cricket Acheta domesticus was examined. During transfer, the male cerci were held close to the female abdomen where they produced small flicking movements. Male cercal ablation significantly decreased mating success by reducing both the ability of the male to hook the epiphallus on to the female subgenital plate and to transfer the spermatophore. During spermatophore transfer, the male must thread the spermatophore tube into the female genital papilla and attach the spermatophore, via its attachment plate, to the base of the ovipositor. Extracellular recordings from the male genital nerve revealed that a centrally driven, rhythmic bursting activity of genital efferents produced the rhythmic contractions of the five pairs of genital muscles responsible for spermatophore threading. Tactile stimulation of campaniform sensilla on the medial aspect of each cercus inhibited the activity of those motor units responsible for advancing the spermatophore tube during threading, while simultaneously activating the motor units responsible for adjusting the position of the epiphallus. We conclude that mechanosensory neurons on the cerci of the male cricket supply important information on female position to the motor program responsible for spermatophore threading and transfer.     

Dunce mutants of Drosophila melanogaster: mutants defective in the cyclic AMP phosphodiesterase enzyme system

The cyclic AMP and cyclic GMP phosphodiesterase activities present in flies of six mutant strains of the dunce gene and in the parent wild-type strains are characterized. All of the mutants exhibit aberrant cyclic AMP metabolism. The mutant strains dunceM14, dunceM11, and dunceML appear to be amorphic, because they completely lack the cAMP-specific phosphodiesterase normally present in adult flies. These strains exhibit extremely high levels of cAMP. The mutant strains dunce1, dunce2, and dunceCK are hypomorphic and exhibit reduced levels of the cAMP-specific phosphodiesterase. These strains exhibit less marked increases in cAMP content compared with the three amorphic strains. The dunce2 strain possesses a residual enzyme activity that exhibits anomalous kinetics compared with those of the normal enzyme. The possibility that the dunce locus is the structural gene for the cAMP-specific phosphodiesterase is discussed.     

Temporal integration in auditory sensory memory: neuromagnetic evidence

The cortical mechanisms of auditory sensory memory were investigated by analysis of neuromagnetic evoked responses. The major deflection of the auditory evoked field (N100m) appears to comprise an early posterior component (N100m^P) and a late anterior component (N100m^A) which is sensitive to temporal factors. When pairs of identical sounds are presented at intervals less than about 250 msec, the second sound evokes N100m^A with enhanced amplitude at a latency of about 150 msec. We suggest that N100m^A may index the activity of two distinct processes in auditory sensory memory. Its recovery cycle may reflect the activity of a memory trace which, according to previous studies, can retain processed information about an auditory sequence for about 10 sec. The enhancement effect may reflect the activity of a temporal integration process, whose time constant is such that sensation persists for 200–300 msec after stimulus offset, and so serves as a short memory store. Sound sequences falling within this window of integration seem to be coded holistically as unitary events.     

The auditory sensory epithelium: the instrument of sound perception

The auditory sensory epithelium is the specialized region of the cochlear epithelium that transduces sound. It is composed of a highly ordered, repeated array of mechanosensory hair cells and nonsensory supporting cells that run along the length of the cochlea. On the apical surface of the hair cells is a specialized structure called the hair bundle that deflects in response to sound vibration, resulting in depolarization of the hair cell and neurotransmitter release. Formation of the auditory sensory epithelium during embryogenesis involves strict control of both cell proliferation and cell patterning. Misregulation of these events can lead to congenital hearing loss, and damage to the auditory sensory epithelium during adult life can lead to adult-onset deafness. This paper reviews recent data on the formation of the auditory sensory epithelium during embryogenesis, the identification of components of the sound transduction apparatus, and advances in the treatment of hearing impairment.     

Melanotic mutants in Drosophila: pathways and phenotypes

Mutations in >30 genes that regulate different pathways and developmental processes are reported to cause a melanotic phenotype in larvae. The observed melanotic masses were generally linked to the hemocyte-mediated immune response. To investigate whether all black masses are associated with the cellular immune response, we characterized melanotic masses from mutants in 14 genes. We found that the melanotic masses can be subdivided into melanotic nodules engaging the hemocyte-mediated encapsulation and into melanizations that are not encapsulated by hemocytes. With rare exception, the encapsulation is carried out by lamellocytes. Encapsulated nodules are found in the hemocoel or in association with the lymph gland, while melanizations are located in the gut, salivary gland, and tracheae. In cactus mutants we found an additional kind of melanized mass containing various tissues. The development of these tissue agglomerates is dependent on the function of the dorsal gene. Our results show that the phenotype of each mutant not only reflects its connection to a particular genetic pathway but also points to the tissue-specific role of the individual gene.     

The role of hypoglossal sensory feedback during feeding in the marine toad, Bufo marinus.

Behavioral observations demonstrate that bilateral deafferentation of the hypoglossal nerves in the marine toad (Bufo marinus) prevents mouth opening during feeding. In the present study, we used high-speed videography, electromyography (EMG), deafferentation, muscle stimulation, and extracellular recordings from the trigeminal nerve to investigate the mechanism by which sensory feedback from the tongue controls the jaw muscles of toads. Our results show that sensory feedback from the tongue enters the brain through the hypoglossal nerve during normal feeding. This feedback appears to inhibit both tonic and phasic activity of the jaw levators. Hypoglossal feedback apparently functions to coordinate tongue protraction and mouth opening during feeding. Among anurans, the primitive condition is the absence of a highly protrusible tongue and the absence of a hypoglossal sensory feedback system. The hypoglossal feedback system evolved in parallel with the acquisition of a highly protrusible tongue in toads and their relatives.     

The role of mitochondria in shaping odor responses in Drosophila melanogaster olfactory sensory neurons

Insects detect volatile chemosignals with olfactory sensory neurons (OSNs) that express olfactory receptors. Among them, the most sensitive receptors are the odorant receptors (ORs), which form cation channels passing also Ca²⁺. Here, we investigate if and how odor-induced Ca²⁺ signals in Drosophila melanogaster OSNs are controlled by intracellular Ca²⁺ stores, especially by mitochondria. Using an open antenna preparation that allows observation and pharmacological manipulation of OSNs we performed Ca²⁺ imaging to determine the role of Ca²⁺ influx and efflux pathways in OSN mitochondria. The results indicate that mitochondria participate in shaping the OR responses. The major players of this modulation are the mitochondrial Ca²⁺ uniporter and the mitochondrial permeability transition pore. Intriguingly, OR-induced Ca²⁺ signals were only mildly affected by modulating the Ca²⁺ management of the endoplasmic reticulum.     

Modulation of prey capture kinematics and the role of lingual sensory feedback in the lizard Pogona vitticeps

Most organisms feed on a variety of prey that may differ dramatically in their physical and behavioural characteristics (e.g. mobility, mass, texture, etc.). Thus the ability to modulate prey capture behaviour in accordance with the characteristics of the food appears crucial. In animals that use rapid tongue movements to capture prey (frogs and chameleons), the coordination of jaws and tongue is based on visual cues gathered prior to the prey capture event. However, most iguanian lizards have much slower tongue-based prey capture systems suggesting that sensory feedback from the tongue may play an important role in coordinating jaw and tongue movements. We investigated the modulation of prey capture kinematics in the agamid lizard Pogona vitticeps when feeding on a range of food items differing in their physical characteristics. As the lizard is a dietary generalist, we expected it to be able to modulate its prey capture kinematics as a function of the (mechanical) demands imposed by the prey. Additionally, we investigated the role of lingual sensory feedback by transecting the trigeminal sensory afferents. Our findings demonstrated that P. vitticeps modulates its prey capture kinematics according to specific prey properties (e.g. size). In addition, transection of the trigeminal sensory nerves had a strong effect on prey capture kinematics. However, significant prey type effects and prey type by transection effects suggest that other sources of sensory information are also used to modulate the prey capture kinematics in P. vitticeps.