The strength of all chemical synapses can be rapidly up- or down-regulated by their recent activities to reshape the postsynaptic signal through a mechanism of short-term facilitation or depression. It is also true that sensory experience is essential for maturation of cortical circuits and function. We studied the effect of sensory experience on the short-term plasticity in brain slices of rat visual cortex. Repetitive stimulation was applied in layer II/III and the response of pyramidal neuron in layer V was examined by whole-cell recording. We deprived the visual experience of rats by rearing the animals in dark environment.We found that dark rearing (DR) had no effects on paired-pulse interactions of either excitatory postsynaptic currents (EPSCs) or inhibitory postsynaptic currents (IPSCs). However, DR increased the level of IPSCs steady-state depression at stimulation frequency of 20 Hz or more. This result, together with the finding that DR reduced the excitability of neural circuit in visual cortex, suggested a compensatory mechanism, which may be important in enhancing the network excitability at a time when synapses are immature.

To elucidate the temperature dependence and underlying thermodynamic determinants of the elementary Ca21 release from the sarcoplasmic reticulum, we characterized Ca21 sparks originating from ryanodine receptors (RyRs) in rat cardiomyocytes over a wide range of temperature. From 35 C to 10 C, the normalized fluo-3 fluorescence of Ca21 sparks decreased monotonically, but the D[Ca21]i were relatively unchanged due to increased resting [Ca21]i. The time-to-peak of Ca21 sparks, which represents the RyR Ca21 release duration, was prolonged by 37% from 35 C to 10 C. An Arrhenius plot of the data identified a jump of apparent activation energy from 5.2 to 14.6 kJ/mol at 24.8 C, which presumably reflects a transition of sarcoplasmic reticulum lipids. Thermodynamic analysis of the decay kinetics showed that active transport plays little role in early recovery but a significant role in late recovery of local Ca21 concentration. These results provided a basis for quantitative interpretation of intracellular Ca21 signaling under various thermal conditions. The relative temperature insensitivity above the transitional 25 C led to the notion that Ca21 sparks measured at a "warm room" temperature are basically acceptable in elucidating mammalian heart function.

Aim: To determine the Ca2+ source and cellular mechanisms of spontaneous Ca2+ oscillations in hippocampal astrocytes. Methods: The cultured cells were loaded with Fluo-4 AM, the indicator of intracellular Ca2+, and the dynamic Ca2+ transients were visualized with confocal laser-scanning microscopy. Results: The spontaneous Ca2+ oscillations in astocytes were observed first in co-cultured hippocampal neurons and astrocytes. These oscillations were not affected by tetrodotoxin (TTX) treatment and kept up in purity cultured astrocytes. The spontaneous Ca2+ oscillations were not impacted after blocking the voltage-gated Ca2+ channels or ethylenediamine tetraacetic acid (EDTA) bathing, indicating that intracellular Ca2+ elevation was not the result of extracellular Ca2+ influx. Furthermore, the correlation between the spontaneous Ca2+ oscillations and the Ca2+ store in endoplasmic reticulum (ER) were investigated with pharmacological experiments. The oscillations were: 1) enhanced when cells were exposed to both low Na+ (70mmol/L) and high Ca2+ (5mmol/L) solution, and eliminated completely by 2 μmol/L thapsigargin, a blocker of sarcoplasmic reticulum Ca2+-ATPase; and 2) still robust after the application with either 50 μmol/L ryanodine or 400 μmol/L tetracaine, two specific antagonists of ryanodine receptors, but depressed in a dose-dependent manner by 2-APB, an InsP3 receptors (InsP3R) blocker. Conclusion: InsP3R-induced ER Ca2+ release is an important cellular mechanism for the initiation of spontaneous Ca2+ oscillation in hippocampal astrocytes.

Subchronic (36 h) exposure of rats to corticosterone (CS) (100 mg/pellet, subcutaneously), blocked the pyrogenic response to recombinant human interleukin 1b (rhIL-1b, 5 mg/kg, ip.). CS treatment reduced the basal mRNA levels of IL-1a and IL-1b, but elevated the mRNA levels of IL-6 in the hypothalamus and hippocampus as shown by RT-PCR. The CS treatment clamped the cytokine mRNA levels, and injection of rhIL-1b to CS treated rats did not significantly affect these altered mRNA levels. IL-6 bioactivity in serum was not significantly changed by CS treatment, but increased 50 times upon injection of rhIL-1b. rhIL-1b caused a significantly lower induction of serum IL-6 levels in CS pretreated rats (9-fold). The pyrogenic response to injection of rhIL-1b has returned 5 days after the removal of the corticosterone pellet, and the hypothalamic cytokine mRNA levels (IL-1a, IL-1b and IL-6) have returned to basal. These results suggest that altered and clamped hypothalamic IL-1a, IL-1b and IL-6 mRNA levels may be involved in the antipyretic effects of a pretreatment with high doses of CS and that these CS effects are rapidly reversible.

Interleukin (IL)-β, IL-β, and tumor necrosis factor 0r (TNF-ot) are considered to act as endogenous pyrogens. Because of the complex pattern of cross-inductions between these cytokines, the relative role of the central and peripheral production of these cytokines in eliciting the fever response has not yet been clarified. The purpose of this study was to determine the role of IL-Β in the fever response by making use of mice carrying a null mutation in the IL-β gene. The intraperitoneal injections oflipopolysaccharide (LPS) (50bLg/kg) and recombinant murine (rm) IL-β (10 bg/kg), respectively, failed to evoke fever response in IL-β-deficient mice, whereas the same doses of LPS and rmIL-βcaused fever response in wild-type mice. The fever response could be induced in the IL-β-deficient mice by intracerebroventricular injection of recombinant human (rh) IL-β (500 ng/mouse), whereas intracerebroventricular injection of rmlL-β (100 ng/mouse) failed to produce fever response in the IL-β-deficient mice. These results suggest that central IL-Β is a necessary component of the fever response to both endogenous (IL-β) and exogenous (LPS) pyrogens in mice and that IL-β acts downstream from both peripheral and central IL-β.