It is broadly accepted that long-term memory (LTM) is formed sequentially after learning and short-term memory (STM) formation, but the nature of the relationship between early and late memory traces remains heavily debated [1-5]. To shed light on this issue, we used an olfactory appetitive conditioning in Drosophila, wherein starved flies learned to associate an odor with the presence of sugar [6]. We took advantage of the fact that both STM and LTM are generated after a unique conditioning cycle [7, 8] to demonstrate that appetitive LTM is able to form independently of STM. More specifically, we show that (1) STM retrieval involves output from γ neurons of the mushroom body (MB), i.e., the olfactory memory center [9, 10], whereas LTM retrieval involves output from αβ MB neurons; (2) STM information is not transferred from γ neurons to αβ neurons for LTM formation; and (3) the adenylyl cyclase RUT, which is thought to operate as a coincidence detector between the olfactory stimulus and the sugar stimulus [11-14], is required independently in γ neurons to form appetitive STM and in αβ neurons to form LTM. Taken together, these results demonstrate that appetitive short- and long-term memories are formed and processed in parallel.

Background-Reperfusion during acute myocardial infarction remains the best treatment for reducing infarct size.Postconditioning, applied at the onset of reperfusion, reduces myocardial infarction both in animals and humans. The objective of this study was to identify the time delay to apply postconditioning at reperfusion, allowing preservation of cardioprotection in the mouse myocardium. This is a major issue in the management of acute myocardial infarction patients. Methods and Results-Mice were subjected to 40 minutes of ischemia and 60 minutes of reperfusion (IR 60Ј ).Postconditioning protocols corresponding to repetitive ischemia (3 cycles of 1 minute of ischemia and 1 minute of reperfusion) were applied during early reperfusion at various time durations (⌬t) after reopening of the coronary artery (⌬tϭ10 seconds, 1,5,10,15,20, 30, and 45 minutes; PostC ⌬t ). Infarct size/area at risk was reduced by 71% in PostC ⌬1 compared with IR 60Ј mice (Pϭ5ϫ10 Ϫ6 ). There was a linear correlation (r 2 ϭ0.91) between infarct size and ⌬t, indicating that the cardioprotective effect of delayed postconditioning was progressively attenuated when ⌬t time increased. The protective effect of PostC ⌬1 and PostC ⌬15 was still effective when the duration of reperfusion was prolonged to 24 hours (IR 24 hours ; PostC ⌬1 and PostC ⌬15 versus IR 24 hours , Pϭ0.001). Similar results were obtained for internucleosomal DNA fragmentation and lactate dehydrogenase release. Key Words: apoptosis Ⅲ ischemia Ⅲ myocardial infarction Ⅲ postconditioning Ⅲ reperfusion injury A cute myocardial infarction is a major cause of heart failure and death. Rapid reperfusion of the ischemic myocardium, by either thrombolysis or primary percutaneous coronary intervention, remains the best treatment for attenuating myocardial infarction. However, reperfusion itself has the potential to initiate additional lethal injury. This deleterious phenomenon culminates in death of cardiac cells that were viable immediately before myocardial reperfusion. 1 New strategies that directly target the reperfusion phase could improve clinical outcomes of acute myocardial infarction. [2][3][4] One such strategy, first described by Zhao and colleagues, 5 is called postconditioning. Applying intermittent episodes of myocardial ischemia/reperfusion at the early moments of reperfusion reduces myocardial infarction in every animal species tested, including mice. 6 Similar beneficial effects were recently demonstrated in patients who underwent primary percutaneous coronary intervention for acute coronary occlusion. 3,4 Conclusions-This Editorial see p 1315 Clinical Perspective on p 1336There appears to be a consensus that the delay after which the first reocclusion is established can only be short, but the available data are surprisingly sparse. 7 In a rat model, the beneficial effect of postconditioning was reported as lost when the delay between reperfusion and the first reocclusion was shifted from 10 to 60 seconds. 8 Since then, postconditioning maneuvers were initiated within 1 ...

The microtubule-associated protein Tau is found in large amount in axons of neurons and is involved in human neurodegenerative diseases called tauopathies, which include Alzheimer's disease. In these diseases, the Tau protein is abnormally hyperphosphorylated and one therapeutic strategy currently under consideration consists in inhibiting Tau phosphorylation. However, the consequences of an excess of hypophosphorylated Tau onto neuronal physiology have not been investigated in vivo. Here we studied how important is Tau phosphorylation for axonal transport and neurohormone release in vivo, using the Drosophila model. Surprisingly, our results demonstrate a stronger toxicity of hypophosphorylated Tau for neuronal function, when compared with normal or pseudophosphorylated Tau. This reveals a potential limit of the current therapeutic strategy aimed at inhibiting Tau phosphorylation.

The remodelling of neurons during their development is considered necessary for their normal function. One fundamental mechanism involved in this remodelling process in both vertebrates and invertebrates is axon pruning. A well-documented case of such neuronal remodelling is the developmental axon pruning of mushroom body γ neurons that occurs during metamorphosis in Drosophila. The γ neurons undergo pruning of larval-specific dendrites and axons at metamorphosis, followed by their regrowth as adult-specific dendrites and axons. We recently revealed a molecular cascade required for this pruning. The nuclear receptor ftz-f1 activates the expression of the steroid hormone receptor EcR-B1, a key component for γ remodelling, and represses expression of Hr39, an ftz-f1 homologous gene. If ectopically expressed in the γ neurons, HR39 inhibits normal pruning, probably by competing with endogenous FTZ-F1, which results in decreased EcR-B1 expression. The mushroom bodies are a bilaterally symmetric structure in the larval and adult brain and are involved in the processing of different types of olfactory memory. How memory is affected in pruning-deficient adult flies that possess larval-stage neuronal circuitry will help to explain the functional role of neuron remodelling. Flies overexpressing Hr39 are viable as adults and make it possible to assess the requirement for wild-type mushroom body pruning in memory. While blocking mushroom body neuron remodelling impaired memory after short-term courtship conditioning, long-term memory was normal. These results show that larval pruning is necessary for adult memory and that expression of courtship short-term memory and long-term memory may be parallel and independent.