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In the past, two main theories of prefrontal function in animals have been proposed. The first implicates the prefrontal cortex in working memory, the second in the inhibitory control of behaviour. However, to date the organisation of the prefrontal cortex in the control of these functions is largely unknown. To address the issue of functional organisation within the prefrontal cortex of the marmoset, this thesis focused on the inhibitory control of behaviour. The initial study demonstrated that attentional set-shifting and visual discrimination reversal learning are sensitive to global prefrontal damage in the marmoset in a qualitatively similar manner to that observed previously in man and Old World monkeys respectively. The deficit was interpreted to be one of inhibitory control but, given the cognitive processing demands of these two tasks are different from one another, it is highly probable that the type of inhibitory control required is also different. Subsequently, the effects of discrete lesions specific to either the lateral or orbital regions of the prefrontal cortex on performance of attentional set-shifting and discrimination reversal learning were examined. Whereas the lateral, but not the orbital, prefrontal cortex was the critical locus in <I>shifting</I> an attentional set between perceptual dimensions; in contrast, the orbital, but not the lateral, prefrontal cortex was the critical locus in <I>reversing</I> a stimulus-reward association within a particular perceptual dimension. Both deficits were interpreted as constituting disinhibition or loss of inhibitory control, but a different levels. The inhibitory control required in attentional set-shifting appears to be at the level of attentional selection whereas the inhibitory control required in reversal learning is likely to be at the level of stimulus-reward associations or 'affective' processing.

The heart develops from a linear tubular precursor, which loops to the right and undergoes terminal differentiation to form the multi-chambered heart. Heart looping is the earliest manifestation of left-right asymmetry, and determines the eventual heart situs. The signalling processes that impart laterality to the unlooped heart tube are poorly understood. Bone Morphogenetic Protein 4 (BMP4) signalling has been shown to be important at a number of points in heart development. Genetic examination of zebrafish development has shown that BMP4 expression, normally left sided, is perturbed in mutants with altered direction of heart looping and situs. This project seeks to elucidate the control of heart looping by BMP4 by studying possible upstream and downstream factors in a putative cascade regulating heart looping, and the effects of BMP4 misexpression on the heart tube itself. I have shown that, in common with zebrafish, BMP4 is expressed predominantly on the left of the <I>Xenopus</I> linear heart tube. I also demonstrate that ectopic expression of <I>nodal</I> RNA upregulates BMP4 expression, linking asymmetric BMP4 expression to the left-right axis. I have used the <I>Xenopus</I> <I>laevis</I> transgenic methodology to manipulate the BMP4 pathway during heart looping morphogenesis, and show that transgenic embryos overexpressing BMP4 bilaterally in the heart tube demonstrate randomised heart situs, whereby inhibiting BMP4 signalling by expressing <I>noggin</I> or a truncated, dominant negative BMP4 receptor prevents heart looping. Hence, BMP4 signalling imparts laterality to the heart tube in <I>Xenopus</I> and is also required for the looping process to occur. This BMP4-dependent looping process appears to be independent of chamber formation.

<I>Drosophila melanogaster</I> Malpighian tubules, the fastest transporting epithelia known to date, are an ideal model for studying regulation of fluid secretion. My main discoveries using Oregon R strain tubules were as follows. I showed that ouabain, an inhibitor of Na<SUP>+</SUP>/K<SUP>+</SUP>-ATPase had no effect on tubules' fluid secretion. Octopamine, which stimulates tubules of several other insect species, had no stimulatory effect on these tubules. I discovered that <I>Drosophila</I> tubules are sensitive to much lower concentrations of cAMP than any other known insect. I found differential sensitivity of the posterior and anterior tubules to cAMP. Using radioactive labelling experiments, I found the presence of a cotransporter for cAMP and cGMP on the principal cells' membranes. I proved that tubules are sensitive to very low levels of cGMP. Using membrane permeant analogues of cAMP and cGMP, namely 8-Br-cAMP and 8-Br-cGMP, I discovered that there is a cAMP signalling pathway, but no cGMP pathway, within the secondary "stellate" cells of Oregon R <I>Drosophila melanogaster</I>. I proved that Oregon R tubules are sensitive to extremely low concentrations of cardioacceleratory peptide CAP<SUB>2b</SUB>. I used the recently discovered naturally occurring <I>Drosophila melanogaster</I> mutants with over expressed cGMP-dependent protein kinase ("Forager R") and under expressed cGMP-dependent protein kinase ("Forager S" and "Forager S2") to analyse regulatory mechanisms of fluid secretion. I found that mutants with under expressed cGMP-dependent protein kinase were, in fact, much more responsive to cGMP, to CAP<SUB>2b</SUB> and extremely responsive to cAMP compared with Oregon R tubules. I showed that mutants with over expressed cGMP-dependent protein kinase were less responsive to cGMP, CAP<SUB>2b</SUB> and to cAMP than Oregon R tubules. Thus, both the cAMP and cGMP pathways were affected by the mutation regarding expression of cGMP-dependent protein kinase., I speculate that phosphodiesterase may be affected by under expression or over expression of cGMP-dependent protein kinase, thereby actually overcompensating for the naturally occurring mutation.

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Using a combination of intracellular recording and computer modelling, this thesis explores the mechanisms underlying motion adaptation in identified wide-field neurons of the lobula plate of the dronefly, <I>Eristalis tenax</I>. The responses of the wide-field cells are consistent with them taking input from an array of correlation-based elementary motion detections (EMDs). The prevailing theory of fly motion adaptation proposes that adaptation shortens the delay in the EMDs, tuning the detectors to higher image velocities. Experimental evidence is presented that challenges this hypothesis. In particular, a key prediction of the theory is that the temporal frequency optimum of the wide-field cells should increase following adaptation. However, direct measurement shows little chant in the temporal or spatial frequency optima following adaptation. This demonstrates that motion adaptation does not alter the inherent velocity tuning of the elementary motion detectors. Measurements of contrast-response functions before and after adaptation provide clear evidence for at least two separate adapting mechanisms in the fly motion pathway: an antagonistic after-potential and a reduction in contrast gain. Further experiments demonstrate that these two mechanisms are recruited by different properties of the visual stimulus. The antagonist after-potential is induced by any adapting stimulus that exists the wide-field cell. The contrast gain reduction is only weakly recruited by flicker, but is strongly recruited by motion presented in <I>any</I> direction, even if that stimulus does not excite the wide-field cell.

No description available.