Glucocorticoid receptor and protein/RNA synthesis-dependent mechanisms underlie the control of synaptic plasticity by stress

Learning and memory are exquisitely sensitive to behavioral stress, but the underlying mechanisms are still poorly understood. Because activity-dependent persistent changes in synaptic strength are believed to mediate memory processes in brain areas such as the hippocampus we have examined the means by which stress affects synaptic plasticity in the CA1 region of the hippocampus of anesthetized rats, Inescapable behavioral stress (placement on an elevated platform for 30 min) switched the direction of plasticity, favoring low frequency stimulation-induced decreases in synaptic transmission (long-term depression, LTD), and opposing the induction of long-term potentiation by high frequency stimulation, We have discovered that glucocorticoid receptor activation mediates these effects of stress on LTD and longterm potentiation in a protein synthesis-dependent manner because they were prevented by the glucocorticoid receptor antagonist RU 38486 and the protein synthesis inhibitor emetine. Consistent with this, the ability of exogenously applied corticosterone in non-stressed rats to mimic the effects of stress on synaptic plasticity was also blocked by these agents, The enablement of low frequency stimulation-induced LTD by both stress and exogenous corticosterone was also blocked by the transcription inhibitor actinomycin D, Thus, naturally occurring synaptic plasticity is liable to be reversed in stressful situations via glucocorticoid receptor activation and mechanisms dependent on the synthesis of new protein and RNA, This indicates that the modulation of hippocampus-mediated learning by acute inescapable stress requires glucocorticoid receptor-dependent initiation of transcription and translation.

Mechanisms of H+ modulation of glycinergic response in rat sacral dorsal commissural neurons

Many ionotropic receptors are modulated by extracellular H+. So far, few studies have directly addressed the role of such modulation at synapses. In the present study, we investigated the effects of changes in extracellular pH on glycinergic miniature inhibitory postsynaptic currents (mIPSCs) as well as glycine-evoked currents (I-Gly) in mechanically dissociated spinal neurons with native synaptic boutons preserved. H+ modulated both the mIPSCs and I-Gly, biphasically, although it activated an amiloride-sensitive inward current by itself. Decreasing extracellular pH reversibly inhibited the amplitude of the mIPSCs and I-Gly, while increasing external pH reversibly potentiated these parameters. Blockade of acid-sensing ion channels (ASICs) with amiloride, the selective antagonist of ASICs, or decreasing intracellular pH did not alter the modulatory effect of H+ on either mIPSCs or I-Gly, H+ shifted the EC50 of the glycine concentration-response curve from 49.3 +/- 5.7 muM at external pH 7.4 to 131.5 +/- 8.1 muM at pH 5.5, without altering the Cl- selectivity of the glycine receptor (GlyR), the Hill coefficient and the maximal I-Gly, suggesting a competitive inhibition of I-Gly by H+. Both Zn2+ and H+ inhibited I-Gly. However, H+ induced no further inhibition of I-Gly in the presence of a saturating concentration of Zn2+. In addition, H+ significantly affected the kinetics of glycinergic mIPSCs and I-Gly. It is proposed that H+ and/or Zn2+ compete with glycine binding and inhibit the amplitude of glycinergic mIPSCs and I-Gly. Moreover, binding of H+ induces a global conformational change in GlyR, which closes the GlyR Cl- channel and results in the acceleration of the seeming desensitization of IGly as well as speeding up the decay time constant of glycinergic mIPSCs. However, the deprotonation rate is faster than the unbinding rate of glycine from the GlyR, leading to reactivation of the undesensitized GlyR after washout of agonist and the appearance of a rebound I-Gly. H+ also modulated the glycine cotransmitter, GABA-activated current (I-GABA). Taken together, the results support a 'conformational coupling' model for H+ modulation of the GlyR and suggest that W may act as a novel modulator for inhibitory neurotransmission in the mammalian spinal cord.

Stress enables synaptic depression in CA1 synapses by acute and chronic morphine: Possible mechanisms for corticosterone on opiate addiction

The hippocampus, being sensitive to stress and glucocorticoids, plays significant roles in certain types of learning and memory. Therefore, the hippocampus is probably involved in the increasing drug use, drug seeking, and relapse caused by stress. We have studied the effect of stress with morphine on synaptic plasticity in the CA1 region of the hippocampus in vivo and on a delayed-escape paradigm of the Morris water maze. Our results reveal that acute stress enables long-term depression (LTD) induction by low-frequency stimulation (LFS) but acute morphine causes synaptic potentiation. Remarkably, exposure to an acute stressor reverses the effect of morphine from synaptic potentiation ( similar to 20%) to synaptic depression ( similar to 40%), precluding further LTD induction by LFS. The synaptic depression caused by stress with morphine is blocked either by the glucocorticoid receptor antagonist RU38486 or by the NMDA-receptor antagonist D-APV. Chronic morphine attenuates the ability of acute morphine to cause synaptic potentiation, and stress to enable LTD induction, but not the ability of stress in tandem with morphine to cause synaptic depression. Furthermore, corticosterone with morphine during the initial phase of drug use promotes later delayed-escape behavior, as indicated by the morphine-reinforced longer latencies to escape, leading to persistent morphine-seeking after withdrawal. These results suggest that hippocampal synaptic plasticity may play a significant role in the effects of stress or glucocorticoids on opiate addiction.

Genetic status of selected fish taxa in relation to conservation of genetic and species diversity in the Victoria and Kyoga Lake basins

Cichlids are known for their explosive radiation especially in the African Great Lakes marked with a high level of lake endemism. These fishes have been characterized mainly along trophic and habitat differences, by variation in morphological structures such as teeth and jaws and by differences in body shape and coloration. Cichlids are important as a microcosm of macroevolution. The explosive radiation, young evolutionary scale, and the isolation of groups characterized with high levels of endemism and presence of living fossils makes the group important for evolutionary and genetic studies. Lake Victoria region cichlids which are isolated and relatively more recent in evolution were the last to be appreciated in their diversity. Recently Ole Seehausen has found scores of rock fishes in Lake Victoria which were up to then thought to be absent from the Lake and only known to occur in Lakes Malawi and Tanganyika. Greenwood put together the species groups of Lake Victoria, and later in the early 1980's revised the classification of haplochromine species to reflect the phyletic origin and interrelationship of the various groups in Lake Victoria region. Melan Stiassny has been interested in early evolution of cichlids while the likes of Paul Fuerst and Lees Kaufman and Axel Meyer have been interested and are working to explain the speciation mechanisms responsible for the explosive radiation and evolution of cichlids. Locally S.B Wandera and his student Getrude Narnulemo are spearheading the biodiversity and taxonomic studies of cichlids in Lake Victoria region

Computational mechanisms of sensorimotor control.

In order to generate skilled and efficient actions, the motor system must find solutions to several problems inherent in sensorimotor control, including nonlinearity, nonstationarity, delays, redundancy, uncertainty, and noise. We review these problems and five computational mechanisms that the brain may use to limit their deleterious effects: optimal feedback control, impedance control, predictive control, Bayesian decision theory, and sensorimotor learning. Together, these computational mechanisms allow skilled and fluent sensorimotor behavior.

Eccentricity effects on acoustic radiation from a spherical source suspended within a thermoviscous fluid sphere.

Acoustic radiation from a spherical source undergoing angularly periodic axisymmetric harmonic surface vibrations while eccentrically suspended within a thermoviscous fluid sphere, which is immersed in a viscous thermally conducting unbounded fluid medium, is analyzed in an exact fashion. The formulation uses the appropriate wave-harmonic field expansions along with the translational addition theorem for spherical wave functions and the relevant boundary conditions to develop a closed-form solution in form of infinite series. The analytical results are illustrated with a numerical example in which the vibrating source is eccentrically positioned within a chemical fluid sphere submerged in water. The modal acoustic radiation impedance load on the source and the radiated far-field pressure are evaluated and discussed for representative values of the parameters characterizing the system. The proposed model can lead to a better understanding of dynamic response of an underwater acoustic lens. It is equally applicable in miniature transducer analysis and design with applications in medical ultrasonics.