One method for exploring neurobiology is to build analogue integrated, circuits which are then used as models for developing and testing theories of the brain. The original motivation for the use of analogue integrated circuits was the concept of a physical equivalence between field-effect transistors operating in the weak-inversion region and ion channels permitting ion conductance through the neuronal membrane. The concept of physical equivalence is examined, with respect to both the physical processes occurring in ion channels and transistors and the equivalences that can be found between neurobiology and models of neurobiology. Changes in ion conductance are the basis for the transmission of electrical impulses in neurons and nervous systems. For the transmission to benefit, or at least not harm, the chances of survival for the organism's genetic material, it must be capable of adapting to changing environment. It has been suggested that ion channels undergoing electrokinesis along the neuronal membrane are a component of intraneuronal adaptation. Analogue integrated circuitry is built to represent the neuronal membrane, a population of dendritic N-type Ca<SUP>++</SUP> channels and intraneuronal adaptation. This is used to link the electrokinesis theory with recent observations of ion channel behaviour, specifically the ion channel gating mechanism, gating modes and transitions between them. The effect of gating in ion channels on the overall output of a neuron is examined and the circuitry is shown to perform a simple adaptation task.

Life history assays were performed on lines of <i>C. elegans</i> in which spontaneous mutations had been allowed to accumulate for 60 generations (Keightley and Caballero, 1997), using a range of harsh conditions. However, no significant degree of genotype by environment interaction was observed. Under some harsher experimental conditions, estimates of mutation rates increased, but the difference was not significant and these results do not lend support to the theory that differences in estimates of mutational parameters are due to variation in assay conditions. Even harsh conditions may not reveal the effects of all mutations that have accumulated and are deleterious in natural conditions, and the extent to which this may result in underestimation of the mutation rate has been unknown. I have measured the effects of EMS-induced mutations on a series of life history traits in <i>C. elegans</i>, in a situation where the number of mutational events induced has been calibrated from studies of suppressor-induced reversion mutations and forward mutations. None of the assays revealed the effects of more than ~ 10% of the deleterious mutations induced, indicating that standard mutation-accumulation experiments may have dramatically underestimated the rate at which mutations accumulate. Such mutations, although cryptic, may nonetheless be significant for evolutionary biology. Two of the lines were further analysed using an inbred-backcross approach, which provided confirmation that only a very small proportion of the induced mutations could be detected. The joint effects of induced mutations on longevity and productivity were also considered. Mortality curves were observed to flatten with age, and this was more notable among the EMS than control lines. One explanation for this was greater heterogeneity among the EMS lines, although other possible causes are discussed. Overall, bivariate analysis revealed strong, positive correlations between longevity and productivity traits, although one line showed a significant increase in longevity, and a correlated decline in early (but not total) productivity, as predicted by the optimality theory of ageing.

I collected 19 pregnant, wild red deer hinds (females) over 14 February to 25 May, 1973, to investigate the extreme weight losses which then occur, since these seem to exemplify the poor productivity of Highland deer populations. Twenty-nine foetuses also were collected, from 18 January to 25 May, the last 19 being those of the collected hinds. Both hinds and foetuses were analysed by physical dissection and chemical composition determinations, and the results are presented and discussed. An experiment was undertaken to measure the productive response of wild hinds to being winter-fed with a high-energy diet; because only one fed hind could be recovered for analysis the experiment was inconclusive. This research and other recent published work lead me to the conclusion that Highland red deer are well adapted to living off body energy reserves in winter, and that level of summer dietary energy intake probably is the most important single factor presently inhibiting Highland red deer productivity.

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This thesis examines extracellular afterpotentials in the retina of Drosophila melanogaster. The results presented, and comparison of these with the available intracellular recordings, indicate that the ERG of Drosophila is a scaled down version of the transmembrane potentials of classes of retinula cells. The afterpotentials investigated are due to retinula cells R1-R6. Afterpotentials in photoreceptors are known to be associated with bi-stable visual pigments. Evidence is presented which suggests that the prolonged depolarising afterpotential (PDA) of R1-R6 in Drosophila results from a component of the membrane conductance of those cells which is correlated with the quantity of metarhodopsin (M580) generated by a stimulus. A simulation, using a membrane model and assuming the M580-conductance, predicts a number of the experimental findings: for example, a high negative correlation between the ERG d.c. potential and the size of the ERG response to a testflash, and a aignoidal decline of the d.c. potential when M580 is eliminated by longwave-length light. The simulation also predicts effects upon the classic V-log I curve which are detected in the Calliphora data of Razmjoo and Hamdorf (1976). Some of the phenomena of the FDA reported in other species (Limulus polyphemus) can only be replicated in Drosophila after small doses of blue light which induce "brief afterpotentials". These phenomena (decay of the afterpotential independently of the decay of metarhodopsin and suppression of the afterpotential by previoss metarhodopsin to rhodopsin conversion) have been taken by others as evidence for an "excitor-inhibitor" model of phototransduction. The value of this model is questioned and a biophysical model of the events in the Drosophila photoreceptors is presented. The afterpotential is shown to occur in wildtype (red eyed) Drosophila, and to have behavioural consequences. A model of extracellular potentials based on capacitance is advanced. This may shed light on electrical potentials in entracellular compartments such as the retina of insects.

The mechanism of sex determination and the development control of the life-cycle of the gastro-intestinal parasite, <i>Strongyloides ratti</i> was investigated using a combination of genetic and parasitological techniques. Parasitological analysis investigated the effects of intra- and extra-host factors on the development of the free-living phase of the life cycle. An initial analysis of the distribution of infective stages among host faecal pellets showed that they were significantly overdispersed and well described by the negative binomial distribution. This overidspersion was found to occur over a wide range of infection intensities and to increase significantly during infection. Further investigation, coupled with an artificial selection experiment, suggested the existence of two discrete developmental switches; an intra-host sex determination switch and an extra-host free-living female/directly developing iL3 development conversion. Analysis of the effects of host immunity on these developmental switches clarified the way in which the composition of the free-living phase varies over the course of an infection. Increasing host immunity results in a greater proportion of female larvae developing into free-living females rather than into directly developing iL3s. Further evidence suggested that the increase in proportion of female larvae that develop into free-living females with increased host immunity is due to an increased temperature sensitivity of the free-living female/directly developing iL3 developmental conversion. Increasing host immunity also alters the sex ratio, resulting in a greater proportion of larvae developing into free-living males. In addition, increased parasitic female age appears to increase the proportion of larvae that develop into free-living males, but does not increase the proportion of female larvae that develop into free-living females. In conclusion, this thesis has used a combined parasitological and genetic approach to investigate the mechanism of sex determination of <i>S. ratti</i>. This understanding now allows a rational view of the <i>S. ratti </i> life-cycle to be presented. These findings are discussed in relation to previous studies of <i>Strongyloides spp.</i> and further questions raised by this work are discussed.

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