Na+/K+-pump is an electrogenic transmembrane ATPase located in the outer plasma membrane of cells. The Na+/K+-ATPase pumps 3 sodium ions out of cells while pumping 2 potassium ions into cells. Both cations move against their concentration gradients. This enzyme’s electrogenic nature means that it has a chronic role in stabilizing the resting membrane potential of the cell, in regulating the cell volume and in the signal transduction of the cell. This review will mainly consider the role of the Na+/K+-pump in neurons, with an emphasis on its role in modulating neurotransmitter receptor. Most of the literature on the modulation of neurotransmitter receptors refers to the situation in the mammalian nervous system, but the position is likely to be similar in most, if not all, invertebrate nervous systems.

Oxytocin has a conserved role in regulating animal social behaviour including parental-offspring interactions. Recently an oxytocin-like neuropeptide, nematocin, and its cognate receptors have been identified in the nematode Caenorhabditis elegans. We provide evidence for a pheromone signal produced by C. elegans larvae that modifies the behaviour of adult animals in an oxytocin-dependent manner increasing their probability of leaving a food patch which the larvae are populating. This increase is positively correlated to the size of the larval population but cannot be explained by food depletion nor is it modulated by biogenic amines, which suggest it is not an aversive behaviour. Moreover, the food-leaving behaviour is conspecific and pheromone dependent: C. elegans adults respond more strongly to C. elegans larvae compared to other nematode species and this effect is absent in C. elegans daf-22 larvae which are pheromone deficient. Neurotransmitter receptors previously implicated in C. elegans foraging decisions NPR-1 and TYRA-3, for NPY-like neuropeptides and tyramine respectively, do not appear to be involved in oxytocin-dependent adult food-leaving. We conclude oxytocin signals within a novel neural circuit that regulates parental-offspring social behaviour in C. elegans and that this provides evidence for evolutionary conservation of molecular components of a parental decision making behaviour.

The nematode Caenorhabditis elegans has a very well-defined and genetically tractable nervous system which offers an effective model to explore basic mechanistic pathways that might be underpin complex human neurological diseases. Here, the role C. elegans is playing in understanding two neurodegenerative conditions, Parkinson's and Alzheimer's disease (AD), and a complex neurological condition, autism, is used as an exemplar of the utility of this model system. C. elegans is an imperfect model of Parkinson's disease because it lacks orthologues of the human disease-related genes PARK1 and LRRK2 which are linked to the autosomal dominant form of this disease. Despite this fact, the nematode is a good model because it allows transgenic expression of these human genes and the study of the impact on dopaminergic neurons in several genetic backgrounds and environmental conditions. For AD, C. elegans has orthologues of the amyloid precursor protein and both human presenilins, PS1 and PS2. In addition, many of the neurotoxic properties linked with Aβ amyloid and tau peptides can be studied in the nematode. Autism spectrum disorder is a complex neurodevelopmental disorder characterised by impairments in human social interaction, difficulties in communication, and restrictive and repetitive behaviours. Establishing C. elegans as a model for this complex behavioural disorder is difficult; however, abnormalities in neuronal synaptic communication are implicated in the aetiology of the disorder. Numerous studies have associated autism with mutations in several genes involved in excitatory and inhibitory synapses in the mammalian brain, including neuroligin, neurexin and shank, for which there are C. elegans orthologues. Thus, several molecular pathways and behavioural phenotypes in C. elegans have been related to autism. In general, the nematode offers a series of advantages that combined with knowledge from other animal models and human research, provides a powerful complementary experimental approach for understanding the molecular mechanisms and underlying aetiology of complex neurological diseases.

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