Striatal dopamine release tracks the relationship between actions and their consequences.

The acquisition and performance of goal-directed actions has long been argued to depend on the integration of glutamatergic inputs to the posterior dorsomedial striatum (pDMS) under the modulatory influence of dopamine. Nevertheless, relatively little is known about the dynamics of striatal dopamine during goal-directed actions. To investigate this, we chronically recorded dopamine release in the pDMS as rats acquired two actions for distinct outcomes as these action-outcome associations were incremented and then subsequently degraded or reversed. We found that bilateral dopamine release scaled with action value, whereas the lateralized dopamine signal, i.e., the difference in dopamine release ipsilaterally and contralaterally to the direction of the goal-directed action, reflected the strength of the action-outcome association independently of changes in movement. Our results establish, therefore, that striatal dopamine activity during goal-directed action reflects both bilateral moment-to-moment changes in action value and the long-term action-outcome association.

Activation of epithelial Na(+) channel activity in the rabbit urinary bladder by cAMP.

The rabbit urinary bladder actively absorbs Na(+) from the urine. The rate-limiting step in this process is the diffusion of Na(+) across the apical membrane of bladder epithelial cells, mediated by amiloride-sensitive epithelial Na(+) channels. We have investigated the effects of cAMP on epithelial Na(+) channel activity in the rabbit bladder by measuring the amiloride-sensitive short-circuit current across bladders mounted in Ussing chambers. Three agents that raise intracellular cAMP levels (forskolin, dibutyryl-cAMP and 3-isobutyl-1-methylxanthine (IBMX)) increased the amiloride-sensitive short-circuit current relative to control preparations. The forskolin-induced increase in amiloride-sensitive short-circuit current was significantly inhibited by the vesicle fusion inhibitor brefeldin A and the protein synthesis inhibitor cycloheximide. These findings, together with the magnitude and protracted time course of the cAMP effects, suggests that cAMP stimulates the insertion of new Na(+) channels into the apical membrane of the rabbit bladder epithelium.

ATP is released from rabbit urinary bladder epithelial cells by hydrostatic pressure changes--a possible sensory mechanism?

1. The responses of rabbit urinary bladder to hydrostatic pressure changes and to electrical stimulation have been investigated using both the Ussing chamber and a superfusion apparatus. These experiments enabled us to monitor changes in both ionic transport across the tissue and cellular ATP release from it. 2. The urinary bladder of the rabbit maintains an electrical potential difference across its wall as a result largely of active sodium transport from the urinary (mucosal) to the serosal surface. 3. Small hydrostatic pressure differences produced by removal of bathing fluid from one side of the tissue caused reproducible changes in both potential difference and short-circuit current. The magnitude of these changes increases as the volume of fluid removed increases. 3. Amiloride on the mucosal (urinary), but not the serosal, surface of the membrane reduces the transepithelial potential difference and short-circuit current with an IC50 of 300 nM. Amiloride reduces the size of, but does not abolish, transepithelial potential changes caused by alterations in hydrostatic pressure. 4. Field electrical stimulation of strips of bladder tissue produces a reproducible release of ATP. Such release was demonstrated to occur largely from urothelial cells and is apparently non-vesicular as it increases in the absence of calcium and is not abolished by tetrodotoxin. 5. It is proposed that ATP is released from the urothelium as a sensory mediator for the degree of distension of the rabbit urinary bladder and other sensory modalities.

Circulating Charcot-Leyden crystals in the hypereosinophilic syndrome.

A patient who had malignant melanoma associated with the hypereosinophilic syndrome died of cardiovascular thrombotic lesions. Widespread tissue eosinophilia was accompanied by numerous Charcot-Leyden crystals in the tumor as well as in various organs, including the renal tubules. A unique observation, not previously described, is the finding of Charcot-Leyden crystals in the thrombi and vessels, including the renal glomeruli. While little is known of the significance of Charcot-Leyden crystals, it is speculated that the circulating crystals injure the endothelium and trigger intravascular coagulation, resulting in thrombosis. A search for the crystals in blood and/or urine may be of additional aid in the evaluation of the extent of the thrombotic process. A special staining method is proposed to facilitate recognition of the crystals, since these are virtually not visualized by routine stain. With the use of such a staining method, future observations in other cases of the hypereosinophilic syndrome may elucidate the role of Charcot-Leyden crystals in the pathogenesis of the thrombotic cardiovascular lesions of this syndrome.