Our study uses a combination of molecular-genetic tools to (1) generate genomic mutations of the dNR1 gene, (2) rescue the accompanying learning deficit with a dNR1+ transgene, and (3) rapidly and transiently knockdown dNR1+ expression in adults, thereby demonstrating an evolutionarily conserved role for the acute involvement of NMDARs in associative learning and memory.
Long-term memory (LTM) depends on the synthesis of new proteins. Using a temperature-sensitive ribosome-inactivating toxin to acutely inhibit protein synthesis, we screened individual neurons making new proteins after olfactory associative conditioning in Drosophila. Surprisingly, LTM was impaired after inhibiting protein synthesis in two dorsal-anterior-lateral (DAL) neurons but not in the mushroom body (MB), which is considered the adult learning and memory center. Using a photoconvertible fluorescent protein KAEDE to report de novo protein synthesis, we have directly visualized cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB)-dependent transcriptional activation of calcium/calmodulin-dependent protein kinase II and period genes in the DAL neurons after spaced but not massed training. Memory retention was impaired by blocking neural output in DAL during retrieval but not during acquisition or consolidation. These findings suggest an extra-MB memory circuit in Drosophila: LTM consolidation (MB to DAL), storage (DAL), and retrieval (DAL to MB).
An ongoing project explores the extent to which artificial intelligence (AI), specifically in the areas of natural language processing and semantic reasoning, can be exploited to facilitate the studies of science by deploying software agents equipped with natural language understanding capabilities to read scholarly publications on the web. The knowledge extracted by these AI agents is organized into a heterogeneous graph, called Microsoft Academic Graph (MAG), where the nodes and the edges represent the entities engaging in scholarly communications and the relationships among them, respectively. The frequently updated data set and a few software tools central to the underlying AI components are distributed under an open data license for research and commercial applications. This paper describes the design, schema, and technical and business motivations behind MAG and elaborates how MAG can be used in analytics, search, and recommendation scenarios. How AI plays an important role in avoiding various biases and human induced errors in other data sets and how the technologies can be further improved in the future are also discussed.
In humans and many other animals, memory consolidation occurs through multiple temporal phases and usually involves more than one neuroanatomical brain system. Genetic dissection of Pavlovian olfactory learning in Drosophila melanogaster has revealed multiple memory phases, but the predominant view holds that all memory phases occur in mushroom body neurons. Here, we demonstrate an acute requirement for NMDA receptors (NMDARs) outside of the mushroom body during long-term memory (LTM) consolidation. Targeted dsRNA-mediated silencing of Nmdar1 and Nmdar2 (also known as dNR1 or dNR2, respectively) in cholinergic R4m-subtype large-field neurons of the ellipsoid body specifically disrupted LTM consolidation, but not retrieval. Similar silencing of functional NMDARs in the mushroom body disrupted an earlier memory phase, leaving LTM intact. Our results clearly establish an anatomical site outside of the mushroom body involved with LTM consolidation, thus revealing both a distributed brain system subserving olfactory memory formation and the existence of a system-level memory consolidation in Drosophila.Pavlovian olfactory learning in Drosophila creates an elemental associative memory in a simple, accessible insect brain. This form of behavioral plasticity requires the normal function of NMDARs 1 , as is the case in other invertebrate and vertebrate species 2,3 . Memory formation in flies thereafter proceeds through several temporal phases and involves multiple biochemical cascades, which is again similar to findings from other animal models 4-6 . In particular, spaced training produces stronger, longer-lasting memory than massed training, which is a common property of memory formation 7,8 . Contrary to the fact that memory storage involves multiple anatomical regions in other animal models 9 , olfactory memory has been proposed to be stored predominantly in the mushroom body neurons 5,10 .The mushroom body is a prominent neuropillar structure in the insect central brain. Intrinsic mushroom body cells send neurites ventrally into the calyx, a region of dendritic arborization that is innervated by efferents from several different regions, including projection neurons from the antennal lobes 11 . Mushroom body axons project rostrally as a densely packed and stalk-like structure called the pedunculus to the anterior face of the brain, where they split and give rise to the dorsally projecting a and a¢ lobes and the medially projecting b, b¢ and g lobes 12 . Output neurons from the mushroom body project to many parts of the central brain. Another prominent neuropil is the central complex, which consists of four substructures, the ellipsoid body, the fan-shaped body, the nodulii and the protocerebral bridge. The central complex lies in the central brain between the pedunculi of the mushroom body and is bounded laterally by the two antennoglomerular tracts, dorsally by the pars intercerebralis, ventrally by the esophagus and the great commissure and frontally by the median bundle and the b-lobes of the mushroom bodies fronta...
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