Neuromuscular organization and aminergic modulation of contractions in the Drosophila ovary

Background: The processes by which eggs develop in the insect ovary are well characterized. Despite a large number of Drosophila mutants that cannot lay eggs, the way that the egg is moved along the reproductive tract from ovary to uterus is less well understood. We remedy this with an integrative study on the reproductive tract muscles (anatomy, innervation, contractions, aminergic modulation) in female flies. Results: Each ovary, consisting of 15-20 ovarioles, is surrounded by a contractile meshwork, the peritoneal sheath. Individual ovarioles are contained within a contractile epithelial sheath. Both sheaths contain striated muscle fibres. The oviduct and uterine walls contain a circular striated muscle layer. No longitudinal muscle fibres are seen. Neurons that innervate the peritoneal sheath and lateral oviduct have many varicosities and terminate in swellings just outside the muscles of the peritoneal sheath. They all express tyrosine decarboxylase (required for tyramine and octopamine synthesis) and Drosophila vesicular monoamine transporter (DVMAT). No fibres innervate the ovarioles. The common oviduct and uterus are innervated by two classes of neurons, one with similar morphology to those of the peritoneal sheath and another with repeated branches and axon endings similar to type I neuromuscular junctions. In isolated genital tracts from 3- and 7-day old flies, each ovariole contracts irregularly (12.5 +/- 6.4 contractions/minute; mean +/- 95% confidence interval). Peritoneal sheath contractions (5.7 +/- 1.6 contractions/minute) move over the ovary, from tip to base or vice versa, propagating down the oviduct. Rhythmical spermathecal rotations (1.5 +/- 0.29 contractions/minute) also occur. Each genital tract organ exhibits its own endogenous myogenic rhythm. The amplitude of contractions of the peritoneal sheath increase in octopamine (100 nM, 81% P < 0.02) but 1 mu M tyramine has no effect. Neither affects the frequency of peritoneal sheath contractions. Conclusion: The muscle fibres of the reproductive tract are circular and have complex bursting myogenic rhythms under octopaminergic neuromodulation. We propose a new model of tissue-specific actions of octopamine, in which strengthening of peritoneal sheath contractions, coupled with relaxation of the oviduct, eases ovulation. This model accounts for reduced ovulation in flies with mutations in the octopaminergic system

Computational approaches for understanding the diagnosis and treatment of Parkinson's disease

This study describes how the application of evolutionary algorithms (EAs) can be used to study motor function in humans with Parkinson's disease (PD) and in animal models of PD. Human data is obtained using commercially available sensors via a range of non-invasive procedures that follow conventional clinical practice. EAs can then be used to classify human data for a range of uses, including diagnosis and disease monitoring. New results are presented that demonstrate how EAs can also be used to classify fruit flies with and without genetic mutations that cause Parkinson's by using measurements of the proboscis extension reflex. The case is made for a computational approach that can be applied across human and animal studies of PD and lays the way for evaluation of existing and new drug therapies in a truly objective way

Comparative neuroethology of feeding control in molluscs

Over the last 30 years, many laboratories have examined, in parallel, the feeding behaviour of gastropod molluscs and the properties of the nervous system that give rise to this behaviour. Equal attention to both behavioural and neurobiological issues has provided deep insight into the functioning of the nervous system in generating and controlling behaviour. The conclusions derived from studies on gastropod feeding are generally consistent with those from other systems, but often provide more detailed information on the behavioural function of a particular property of the nervous system. A review of the literature on gastropod feeding illustrates a number of important messages. (i) Many of the herbivorous gastropods display similarities in behaviour that are reflected in corresponding similarities in neural anatomy, pharmacology and physiology. By contrast, the same aspects of the behaviour of different carnivorous species are quite variable, possibly because of their specialised prey-capture techniques. Nonetheless, some aspects of the neural control of feeding are preserved. (ii) Feeding in all species is flexible, with the behaviour and the physiology adapting to changes in the current environment and internal state and as a result of past experience. Flexibility arises via processes that may take place at many neural sites, and much of the modulation underlying behavioural flexibility is understood at a systems and at a cellular level. (iii) Neurones seem to have specific functions that are consistent with their endogenous properties and their synaptic connections, suggesting that individual neurones code specific pieces of information (i.e. they are ‘grandmother cells’). However, the properties of a neurone can be extremely complex and can be understood only in the context of the complete neural circuit and the behaviour that it controls. In systems that are orders of magnitude more complex, it would be impossible to understand the functional properties of an individual neurone, even if it also coded specific information. (iv) Systems such as gastropod feeding may provide a model for understanding the functional properties of more complex systems

Activation and reconfiguration of fictive feeding by the octopamine-containing modulatory OC interneurons in the snail Lymnaea

We describe the role of the octopamine-containing OC interneurons in the buccal feeding system of Lymnaea stagnalis. OC neurons are swallowing phase interneurons receiving inhibitory inputs in the N1 and N2 phases, and excitatory inputs in the N3 phase of fictive feeding. Although the OC neurons do not always fire during feeding, the feeding rate is significantly (P < 0.001) higher when both SO and OC fire in each cycle than when only the SO fires. In 28% of silent preparations, a single stimulation of an OC interneuron evokes the feeding pattern. Repetitive stimulation of the OC interneuron increases the proportion of responsive preparations to 41%. The OC interneuron not only changes both the feeding rate and reconfigures the pattern. Depolarization of the OC interneurons increases the feeding rate and removes the B3 motor neuron from the firing sequence. Hyperpolarization slows it down (increasing the duration of N1 and N3 phases) and recruits the B3 motor neuron. OC interneurons form synaptic connections onto buccal motor neurons and interneurons but not onto the cerebral (cerebral giant cell) modulatory neurons. OC interneurons are electrically coupled to all N3 phase (B4, B4Cl, B8) feeding motor neurons. They form symmetrical connections with the N3p interneurons having dual electrical (excitatory) and chemical (inhibitory) components. OC interneurons evoke biphasic synaptic inputs on the protraction phase interneurons (SO, N1L, N1M), with a short inhibition followed by a longer lasting depolarization. N2d interneurons are hyperpolarized, while N2v interneurons are slowly depolarized and often fire a burst after OC stimulation. Most motor neurons also receive synaptic responses from the OC interneurons. Although OC and N3p interneurons are both swallowing phase interneurons, their synaptic contacts onto follower neurons are usually different (e.g., the B3 motor neurons are inhibited by OC, but excited by N3p interneurons). Repetitive stimulation of OC interneuron facilitates the excitatory component of the biphasic responses evoked on the SO, N1L, and N1M interneurons, but neither the N2 nor the N3 phase interneurons display a similar longer-lasting excitatory effect. OC interneurons are inhibited by all the buccal feeding interneurons, but excited by the serotonergic modulatory CGC neurons. We conclude that OC interneurons are a new kind of swallowing phase interneurons. Their connections with the buccal feeding interneurons can account for their modulatory effects on the feeding rhythm. As they contain octopamine, this is the first example in Lymnaea that monoaminergic modulation and reconfiguration are provided by an intrinsic member of the buccal feeding network

Distance and force production during jumping in wild type and mutant Drosophila melanogaster

In many insects renowned for their jumping ability, elastic storage is used so that high forces can be developed prior to jumping. We have combined physiological, behavioural and genetic approaches to test whether elastic energy storage makes a major contribution to jumping in Drosophila. We describe a sensitive strain gauge setup, which measures the forces produced by tethered flies through their mesothoracic legs. The peak force produced by the main jumping muscle of female flies from a wild-type (Canton-S) strain is 101±4.4 µN [and this is indistinguishable from a second wild-type (Texas) strain]. The force takes 8.2 ms to reach its peak. The peak force is not affected significantly by altering the leg angle (femur–tibia joint angle) in the range of 75–120°, but the peak force declines as the leg is extended further. Measurements of jumping ability (distance jumped) showed that female Drosophila (with their wings removed) of two wild-type strains, Canton-S and Texas, produced jumps of 28.6±0.7 and 30.2±1.0 mm (mean ± S.E.M.). For a female wild-type Drosophila, a jump of 30 mm corresponds to a kinetic energy of 200 nJ on take-off (allowing 20% of the energy to overcome air resistance). We develop equations of motion for a linear force–time model of take-off and calculate that the time to take-off is 5.0 ms and the peak force should be 274 µN (137 µN leg–1). We predicted, from the role of octopamine in enhancing muscle tension in several locust muscles, that if stored elastic energy plays no part in force development, then genetic manipulation of the octopaminergic system would directly affect force production and jumping in Drosophila. Using two mutants deficient in the octopaminergic system, TbhnM18 (M18) and TyrRhono (hono), we found significantly reduced jumping distances (20.7±0.7 and 20.7±0.4 mm, respectively) and force production (52% and 55%, respectively) compared with wild type. From the reduced distance and force production in M18, a mutant deficient in octopamine synthesis, and in hono, a tyramine/octopamine receptor mutant, we conclude that in Drosophila, as in locusts, octopamine modulates escape jumping. We conclude that the fly does not need to store large quantities of elastic energy in order to make its jump because (1) the measured and calculated forces agree to within 40% and (2) the reduction in distances jumped by the mutants correlates well with their reduction in measured peak force