FEEDBACK REGULATION OF 5-HT SYNTHESIS IN RAT STRIATAL SLICES

The effects of changes in intraneuronal levels of 5-HT induced by monoamine oxidase inhibitors (MAOI) given in vivo or exogenous 5-HT added in vitro on 5-HT synthesis in striatal slices of the rat have been examined. The synthesis of 5-HT was estimated by the measurement of the total formation of [³H]5-HT and [³H]5-hydroxyindole acetic acid from [³H]tryptophan and by calculation of the conversion index (CI) of tryptophan into 5-HT. The small formation of [³H]tryptamine and [³H]indole acetic acid from [³H]tryptophan was taken into account in the estimation of 5-HT synthesis. Both MAOI pretreament (180 min) and 5-HT (2·8 μM) inhibited synthesis. The latter effect persisted in catecholamine depleted tissues and was related to intraneuronal changes in 5-HT levels, since it could be prevented by chlorimipramine. The inhibition of 5-HT synthesis was related to the decreased conversion of tryptophan into 5-hydroxytryptophan and could not be prevented by p-chloro-phenylalanine pretreatment which depleted 5-HT levels or by dibutyryl cyclic AMP which normally stimulated 5-HT synthesis. Tryptophan uptake in slices was not affected by exogenous 5-HT. The various mechanisms possibly involved in the end product regulation process of 5-HT synthesis are discussed.     

Location and dynamic properties of the spike generator in an insect mechanosensory neuron

1.The cereal bristle hairs of the cockroach, Periplaneta americana, are each innervated by one mechanosensory cell and 1–5 chemosensory cells. In transepithelial recordings, chemo- and mechanosensory spikes could be discriminated from each other by their relative amplitude. 2. When current steps were applied via the sensory hair, trains of impulses were triggered whatever the polarity of the current. 3. All responses adapted to the current, but the time course of adaptation was fitted by a power law for outward currents and an exponential law for inward currents. 4. During application of outward currents, the spikes showed a negative initial phase on which a small positive component was superimposed; strong polarizations produced purely negative spikes. More classical spikes with a positive initial phase were induced by inward currents. 5. The present work supports the hypothesis of a direct excitability of the apical dendrite in cereal bristle mechanoreceptors and confirms previous results suggesting that spikes are normally triggered within that region during mechanical stimulations. It is also established, for the first time, that adaptation to currents may be different in the apical dendrite and in more basal regions of the same mechanosensory neuron.Abbreviation RP receptor potential - TEV transepithelial voltage - TTX tetrodotoxin     

Listeriolysin O: the Swiss army knife of Listeria

Listeriolysin O (LLO) is a toxin produced by Listeria monocytogenes, an opportunistic bacterial pathogen responsible for the disease listeriosis. This disease starts with the ingestion of contaminated foods and mainly affects immunocompromised individuals, newborns, and pregnant women. In the laboratory, L. monocytogenes is used as a model organism to study processes such as cell invasion, intracellular survival, and cell-to-cell spreading, as this Gram-positive bacterium has evolved elaborate molecular strategies to subvert host cell functions. LLO is a major virulence factor originally shown to be crucial for bacterial escape from the internalization vacuole after entry into cells. However, recent studies are revisiting the role of LLO during infection and are revealing new insights into the action of LLO, in particular before bacterial entry. These latest findings along with their impact on the infectious process will be discussed.     

Pharmacological and Physicochemical Properties of Pre-Versus Postsynaptic 5-Hydroxytryptamine1A Receptor Binding Sites in the Rat Brain: A Quantitative Autoradiographic Study

Numerous data suggested that the pharmacological and biochemical properties of 5-hydroxytryptamine1A (5-HT1A) receptors exhibit some regional differences in the CNS, notably within the raphe nuclei compared with various forebrain areas (such as the hippocampus). This possibility has been further investigated in the dorsal raphe nucleus and two areas within the hippocampus, the dentate gyrus and the CA1 area, using the quantitative autoradiographic technique. The potencies of 5'-guanylylimidodiphosphate to inhibit the specific binding of 125I-Bolton-Hunter-8-methoxy-2-(N-propyl-N-propylamino)tetralin (125I-BH-8-MeO-N-PAT) to 5-HT1A sites and of N-ethylmaleimide to block these sites irreversibly were identical in the dorsal raphe nucleus and the hippocampal areas in rat brain sections. In contrast, slight but significant differences were noted in the pH dependence and pharmacological properties of 5-HT1A sites labeled by 125I-BH-8-MeO-N-PAT in these three regions. Similarly, heat denaturation experiments and tissue exposure to either phospholipase A2 or the alkylating agent 8-methoxy-2-(N-2'-chloropropyl,N-propyl)aminotetraline revealed regional differences in the properties of 5-HT1A sites. However, in most cases, the observed variations were of greater amplitude between the CA1 area and the dentate gyrus, where 5-HT1A sites are located postsynaptically, than between any one of these areas and the dorsal raphe nucleus where they act as (presynaptic) somatodendritic autoreceptors. These data further support that subtypes of 5-HT1A receptors probably exist in the rat brain, but this heterogeneity seems unrelated to the pre- or post-synaptic location of these receptors.     

A gradient of synaptic efficacy and its presynaptic basis in the cercal system of the cockroach

1. The cerci of the cockroach Periplaneta americana bear longitudinal columns of wind-sensitive receptors which provide excitatory inputs to the giant interneurons (GIs) of the abdominal nerve cord. By using sound stimuli, we showed that spikes were more easily induced in the GIs from the most proximal than from the most distal receptors of the same column. 2. This was not due to a greater responsiveness of proximal sensilla to tones but to stronger synaptic connections; for the 3 largest GIs, the amplitude of the monosynaptic unitary EPSP tended to be all the higher as the stimulated sensillum was more proximal in each column. 3. The differences in EPSP size were due, at least partly, to presynaptic factors: a statistical analysis of the amplitude fluctuations of single-fibre EPSPs, showed that the amount of transmitter released per presynaptic impulse was larger for proximal than for distal sensory neurons in each column. 4. These differences in synaptic strength were correlated with differences in the structure of the afferent terminals. The location, the size and the shape of the axonal arbors are nearly the same for all sensory neurons of the same column, but proximal neurons arborize more profusely, and the terminal arbor of distal neurons is generally characterized by dorsal clusters of varicosities. 5. During postembryonic development, a decrease in the connection strength of 2 identified cercal neurons was accompanied by a retraction of ramifications on the medial side of their axonal arbor. 6. Possible mechanisms involved in the genesis and the remodelling of the gradient of synaptic strength are discussed in the light of available data and hypotheses relative to the development of ordered afferent connections.