The functional role of octopaminergic neurons in insect motor behavior

The role of efferent, octopaminergic dorsal unpaired median (DUM) neurons in insects is examined by recording from them during motor behaviour. This population of neuromodulatory neurons is divided into sub-populations which are specifically activated or inhibited during ongoing motor behavior. These neurons are always activated in parallel to the respective motor circuits, and in addition to their modulatory effects on synaptic transmission may also cause metabolic changes in their target tissues.     

Roles of octopaminergic and dopaminergic neurons in appetitive and aversive memory recall in an insect

Background  

In insect classical conditioning, octopamine (the invertebrate counterpart of noradrenaline) or dopamine has been suggested to mediate reinforcing properties of appetitive or aversive unconditioned stimulus, respectively. However, the roles of octopaminergic and dopaminergic neurons in memory recall have remained unclear.     

The Florey lecture, 1986. The regulatory biology of antibody formation

The regulatory biology of antibody formation entered a new phase of study with the development of selective theories of immunity. The discovery of the 'one cell - one antibody' dogma and the demonstration that only a small minority of B cells possessed receptors specific for a given antigen were consistent with Burnet's clonal selection hypothesis, which was later formally proven by preparing antigen-specific lymphocytes and inducing clonal activation in vitro. Clonal analysis has aided precise study of immunoregulation for both B and T lymphocytes. Clonal activation of B cells in the absence of T cells is now possible with high cloning efficiency. It requires the combined action of certain antigens and growth factors, collectively termed B-cell stimulatory factors (BSFS). Single cell analysis has shown that most BSFS so far tested, in contrast to most claims in the literature, possess the capacity (in synergy with antigen) to: stimulate B cells out of the G0 phase into active cell cycle; promote sequential mitotic divisions; and induce differentiation to active secretory status. This is clearly true for IL-1, IL-2, and BSF-p2. These multiple actions resemble those of the colony-stimulating factors in haemopoiesis. Regulation of antibody production by T lymphocytes can also be profitably analysed in clonal systems. The immunoregulatory problem of tolerance can also be analysed by means of clonal techniques. Studies are summarized which indicate that T-cell-mediated suppression and functional silencing of toleragen-specific lymphocytes are both cooperatively involved in many tolerance models. For the B lymphocyte, tolerance can be induced without an actual deletion of the cell involved; rather, the tolerant cell appears to have received and stored a negative signal, rendering it unresponsive to normally immunogenic stimuli. Thus, a state termed 'clonal anergy' has been induced within the cell. Functional clonal deletion has also been noted in several models to T-lymphocyte tolerance, but here it is not known whether clonal anergy or actual death of the relevant cell is at work. Self-tolerance sufficient to be consistent with good health need not mean a total absence of cells with any degree of self-reactivity. Indeed, it is clear that some B cells capable of forming antibody with some degree of affinity for self-constituents exist in the body, and can be activated, for example by lipopolysaccharide. The requirement is to limit the amount, affinity and duration of autoantibody production. A model suggesting how this may be achieved is presented.     

The Florey lecture, 1986. Vaccine prevention of virus-induced human cancers

Carcinogenic viruses have been discovered in numerous animal species over the last 80 years but their role in human cancer has only recently become an important issue. With EB virus involved with endemic Burkitt's lymphoma and undifferentiated nasopharyngeal carcinoma, hepatitis B virus with primary liver cancer, papilloma viruses with carcinoma of the cervix, and T-cell leukaemia virus with adult T leukaemia, 20-25% of all human cancer appears to have a virus component in its causation. By analogy with certain virus-induced animal cancers, vaccine prevention of infection should greatly reduce subsequent tumour development; vaccines against hepatitis B virus are already on trial for this purpose in populations at risk. Experiments are described in which an EB virus subunit vaccine consisting of the virus-determined membrane antigen glycoprotein molecule of molecular mass 340 kDa (MA gp340) has been prepared by two purification methods. Material from one of these has successfully protected cotton-top tamarins against a 100% lymphomagenic dose of challenge virus and investigations are under way to identify an immunogen, based on MA gp340, suitable for use in man. Genetically engineered bacterial, yeast, and mammalian cells expressing the gp340 gene are already available; this gene has also been inserted into vaccinia and varicella virus vectors. Powerful new adjuvants are also considered, together with future strategies for human vaccine studies.     

The Florey lecture, 1989. Self-tolerance: the key to autoimmunity

'Horor autotoxicus', as it was termed by Erhlich, is a rare clinical event despite the genetic potential of every individual to mount immune responses to self-antigens. This can be explained by the fact that the developing immune system learns to recognize self-antigens and to tolerate them. The key to autoimmunity therefore lies in unravelling the mechanisms of self-tolerance. Studies of conventional models of unresponsiveness have failed to provide a definitive answer owing to the difficulty in controlling for the large number of antigen-related variables associated with self-tolerance and in following the fate of individual clones of self-reactive lymphocytes which emerge in very low numbers from the pre-immune repertoire. These problems have now been overcome by creation of transgenic mice tolerant to endogenous antigens and containing high frequencies of autoreactive T or B lymphocytes. According to the results obtained to date, different mechanisms of tolerance induction operate for self-reactive T lymphocytes compared with B lymphocytes. Thus self-tolerance in T lymphocytes appears to depend largely on clonal deletion within the thymus. By contrast, self-reactive B lymphocytes are functionally silenced without undergoing deletion provided that the transgenic B lymphocytes express both IgM and IgD on their surfaces. This dichotomy makes good sense given that the T-lymphocyte repertoire once shaped within the thymus is not subject to further mutation whereas antigen receptors on mature B lymphocytes undergo hypermutation in the periphery.     

The Florey lecture, 1987. Corticomotoneuronal projections: synaptic events related to skilled movement

During infancy, children develop an expanding repertoire of movement skills in parallel with the maturation in their brains of direct nerve-fibre connections between the cerebral cortex and motoneurons in the spinal cord. These corticomotoneuronal connections are characteristic of primates and can be studied in monkeys; in these animals, refinement in the control of movements of the hand is also associated with increasing development of corticomotoneuronal connections. In monkeys, motoneurons innervating distally acting muscles are preferentially excited by convergent activities in corticomotoneuronal fibres. This excitation has been demonstrated to be effective in natural functional states when a conscious monkey is performing learned movement tasks. Extensive intraspinal arborizations of individual corticomotoneuronal fibres could permit the engagement of large numbers of local motoneurons and related interneurons by each of these fibres. Abolition of corticomotoneuronal influences, after section of the pyramidal tracts, causes a permanent deficit in fractionation of use of muscles of the forelimb and an inability to carry out independent movements of the fingers.     

Changes in firing behaviour of an insect motor neurone during development and following experimental surgery

The firing behaviour of an identified neurone in the cricket was studied using extracellular recording from the axon. In the last nympal instar (preadult developmental stage), the contralateral dorsal longitudinal motor neurone (CDLM) showed spontaneous activity and was excited by air puffs to the head and cerci and by single shocks to the anterior nerve cord. In the normal adult the CDLM did not exhibit these properties. However, responses which were characteristic of the last instar appeared in the adults which had been subjected to any one of the following surgical procedures: (1) central nervous system injuries which separated the CDLM arborization and axon from the soma; (2) operations which injured the central nervous system without cutting the CDLM; and (3) operations which damaged the cuticle only. Since cuticle damage alone was as effective as the more extensive operations, it is suggested that a sufficient cause for the appearance of nymphal firing behaviour in the adult CDLM is cuticle damage. The factor associated with cuticle damage which mediates the changes in activity of the CDLM neurone is not known, but its action does not require the mediation of the CDLM soma.     

昆虫肠道菌群的功能研究进展

昆虫肠道为某些微生物提供了一个特定的定殖环境,这些肠道菌群也为其宿主提供了很多潜在的有益作用。因而昆虫在一定范围和程度上表现出对肠道菌群的依赖并形成一种互惠互利的共生关系。近年来,随着高通量测序技术的广泛应用,促进了肠道菌群及其功能基因的研究。也为进一步了解如何区分非致病性菌(共生菌)和致病菌(病原菌)的致病机理、调控昆虫肠道菌并用来防治害虫或保护授粉昆虫在内的有益昆虫奠定了基础。本文概述了昆虫肠道菌群定殖环境、起源和进化以及传播方式,综述了近年来昆虫肠道菌群功能研究的最新进展,并对今后昆虫肠道菌群的研究方向进行了展望。     

The Wellcome Foundation lecture, 1982. Opioid peptides and their receptors

The remarkable feature of the opioid system is the complexity of its ligands and their interactions with the mu-, delta- and kappa-binding sites. The three endogenous opioid precursors give rise to more than ten opioid fragments. The fragments of pro-opiocortin and pro-enkephalin have affinities mainly to the mu- and delta-binding sites and those of pro-dynorphin have a preference for the kappa-binding site. It is important to realize that some of the larger fragments may have pharmacological actions that are of a non-opioid character. As the endogenous opioid peptides bind to more than one of the types of binding sites, it was necessary to obtain synthetic compounds that bind almost exclusively at one site. There are now agonists for which this aim has been achieved but we still require antagonists that are exclusively selective for only one opioid site. The results obtained with opioid peptides or non-peptides having such qualities would be the physiological basis for a correlation of the binding at mu-, delta- and kappa-receptors with their pharmacological effects. Furthermore, since almost all endogenous opioid ligands are degraded by peptidases, it is necessary to synthesize non-toxic inhibitors of those peptidases that play a role in opioid transmission. Related to this problem is the need to develop methods for the study of the release of various endogenous opioid peptides under physiological conditions.     

Interactions between neurons and their targets during in vivo synaptogenesis.

In vivo synaptogenesis is described in a simple vertebrate system, the chick ciliary ganglion, a parasympathetic autonomic ganglion. An attempt is made to integrate anatomical, physiological and biochemical observations during synapse formation in the ganglion and in the peripheral target structures; the iris, ciliary muscle, and smooth muscle of the choroid coat. The relationship between synaptogenesis and neuron survival is explored, and it is shown that a critically timed interaction between the neuron and target organ is necessary for full neuronal maturation and survival. The existence of an active competition between neurons for survival is documented, and the possible relationship between neuronal cell death and specificity of connections is discussed.