Effect of the serotonin agonist buspirone on behaviour and hypothalamic-pituitary-adrenal axis in confident and fearful mink

Behavioural and hypothalamic-pituitary-adrenal (HPA) axis responses were investigated in farm mink (Mustela vison) selected for either confident or fearful behaviour for nine generations.Two groups of 2-year-old confident (n=12) and fearful (n=12) female mink were given the serotonin (5-HT) 1A receptor agonist buspirone (1.25 mg/kg/day), whereas two other groups of 2-year-old confident (n=12) and fearful (n=12) female mink were given saline, continuously for 5 weeks via osmotic minipumps. Behavioural reactions towards a novel object and towards humans were tested after 19-25 days, and HPA axis reactivity [adrenocorticotropic hormone (ACTH), cortisol] was measured after 28-31 days of treatment. Confident mink were more exploratory than fearful mink towards humans and a novel object. Confident mink spent more time in contact with the object than did fearful mink during saline-but not during buspirone-treatment. buspirone increased approach-withdrawal conflict behaviour towards a object in fearful mink only. The chronic dose of buspirone did not reduce fear towards humans and did not affect latencies to reaction, number of contacts, number and duration of manipulations, and stereotypic behaviour in a Novel Object test. Different HPA axis responses have emerged between confident and fearful mink, together with a different degree of fear-related behaviour. Fearful mink have a higher cortisol combined with a lower ACTH secretion than confident mink in response to capture and blood sampling. The central serotonergic system may be involved, and even though the precise underlying mechanisms are presently unknown, treatment with a 5-HT(1A) receptor agonist reduces the difference between confident and fearful mink in HPA axis reactivity.     

Ly6C expression differentiates plasma cells from other B cell subsets in mice.

Plasma cell differentiation is induced in vitro by lipopolysaccharide (LPS) stimulation but can be blocked by including anti-CD40 antibodies. Using subtractive cDNA hybridization we have identified the cell surface protein Ly6C as differentially expressed on B cells stimulated with LPS only. Ly6C has been shown to be expressed on certain T cell subsets and on subsets of macrophages and NK cells, but not on resting B cells. We show that Ly6C is up-regulated upon LPS stimulation of B cells in vitro and that this up-regulation is blocked by anti-CD40 or anti-Ig antibodies. Furthermore, ELISPOT analysis of cells sorted by magnetic-activated cell sorting show that Ly6C is expressed on ex vivo plasma cells from the spleen and bone marrow. Flow cytometric analysis showed that Ly6C is expressed on splenic plasma cells as well as on lamina propria plasma cells. Finally, Ly6C cross-linking positively up-regulated the amount of immunoglobulin produced by LPS-stimulated splenic B cells in vitro.     

Presynaptic control of group Ia afferents in relation to acquisition of a visuo-motor skill in healthy humans

Sensory information continuously converges on the spinal cord during a variety of motor behaviours. Here, we examined presynaptic control of group Ia afferents in relation to acquisition of a novel motor skill. We tested whether repetition of two motor tasks with different degrees of difficulty, a novel visuo-motor task involving the ankle muscles, and a control task involving simple voluntary ankle movements, would induce changes in the size of the soleus H-reflex. The slope of the H-reflex recruitment curve and the H-max/M-max ratio were depressed after repetition of the visuo-motor skill task and returned to baseline after 10 min. No changes were observed after the control task. To elucidate the mechanisms contributing to the H-reflex depression, we measured the size of the long-latency depression of the soleus H-reflex evoked by peroneal nerve stimulation (D1 inhibition) and the size of the monosynaptic Ia facilitation of the soleus H-reflex evoked by femoral nerve stimulation. The D1 inhibition was increased and the femoral nerve facilitation was decreased following the visuo-motor skill task, suggesting an increase in presynaptic inhibition of Ia afferents. No changes were observed in the disynaptic reciprocal Ia inhibition. Somatosensory evoked potentials (SEPs) evoked by stimulation of the tibial nerve (TN) were also unchanged, suggesting that transmission in ascending pathways was unaltered following the visuo-motor skill task. Together these observations suggest that a selective presynaptic control of Ia afferents contributes to the modulation of sensory inputs during acquisition of a novel visuo-motor skill in healthy humans.     

The effect of volume currents due to myocardial anisotropy on body surface potentials

Changes in anterior and posterior body surface potential maps (BSPMs) due to myocardial anisotropy were examined using a highly heterogeneous finite element model of an adult male subject constructed from segmented magnetic resonance images. A total of 23 different tissue types were identified in the whole torso. The myocardial fibre orientations in the human heart wall were mapped from the fibre orientations of a canine heart which are available in the literature using deformable mapping techniques. The current and potential distributions in the whole torso were computed using dipolar sources in the septum, apical area, left ventricular wall or right ventricular wall. For each dipole x, y, z orientations were studied. An adaptive finite element solver was used to compute currents and potential distributions in the whole torso with an element size of 0.78 x 0.78 x 3 mm in the myocardium and larger elements in other parts of the torso. For each dipole position two cases were studied. In one case the myocardium was isotropic and in the other it was anisotropic. It was found that BSPMs showed a very notable difference between the isotropic and the anisotropic myocardium for all dipole positions with the largest difference for the apical dipoles. The correlation coefficients for the BSPMs between the isotropic and anisotropic cases ranged from 0.83 for an apical dipole to 0.99 for an RV wall dipole. These results suggest that myocardial fibre anisotropy plays an important role in determining the body surface potentials.     

Differential localization of IL-2- and -15 receptor chains in membrane rafts of human T cells

We studied whether cytokine receptors (Rs) on T cells associate with lipid microdomains ("rafts"). Low-dose phytohemagglutinin (PHA)-stimulated human T cells were separated into cytoplasmic, membrane, and raft fractions by buoyant density centrifugation. Examination of these fractions for the presence of interleukin (IL)-2- and -15R chains and associated signaling molecules by Western blotting revealed marked, selective enrichment of the IL-2/15R beta-chain in rafts before IL-2 stimulation. After IL-2 stimulation, a substantial amount of the beta-chain was found in the membrane fraction. This partial translocation was also observed for the beta-chain-associated molecules JAK-1, p56(lck), and grb-2. Finally, raft disruption with methyl-beta-cyclodextrin (MBCD) attenuated IL-2-induced tyrosine phosphorylation events and selectively decreased the surface expression of the IL-2/15R beta-chain detected by flow cytometry. These results show that the IL-2/15R beta-chain is enriched in rafts obtained from low-dose, PHA-stimulated T cells, that IL-2 binding alters this enrichment, and that this enrichment may be functionally relevant as a possible mechanism to ensure cytokine selectivity and specificity.