Neural coding for olfactory sensory stimuli has been mapped near completion in the Drosophila first-order center, but little is known in the higher brain centers. Here, we report that the antenna lobe (AL) spatial map is transformed further in the calyx of the mushroom body (MB), an essential olfactory associated learning center, by stereotypic connections with projection neurons (PNs). We found that Kenyon cell (KC) dendrites are segregated into 17 complementary domains according to their neuroblast clonal origins and birth orders. Aligning the PN axonal map with the KC dendritic map and ultrastructural observation suggest a positional ordering such that inputs from the different AL glomeruli have distinct representations in the MB calyx, and these representations might synapse on functionally distinct KCs. Our data suggest that olfactory coding at the AL is decoded in the MB and then transferred via distinct lobes to separate higher brain centers.

Memory is initially labile and gradually consolidated over time through new protein synthesis into a long-lasting stable form. Studies of odor-shock associative learning in Drosophila have established the mushroom body (MB) as a key brain structure involved in olfactory long-term memory (LTM) formation. Exactly how early neural activity encoded in thousands of MB neurons is consolidated into protein-synthesis-dependent LTM remains unclear. Here, several independent lines of evidence indicate that changes in two MB vertical lobe V3 (MB-V3) extrinsic neurons are required and contribute to an extended neural network involved in olfactory LTM: (i) inhibiting protein synthesis in MB-V3 neurons impairs LTM; (ii) MB-V3 neurons show enhanced neural activity after spaced but not massed training; (iii) MB-V3 dendrites, synapsing with hundreds of MB α/β neurons, exhibit dramatic structural plasticity after removal of olfactory inputs; (iv) neurotransmission from MB-V3 neurons is necessary for LTM retrieval; and (v) RNAi-mediated downregulation of oo18 RNA-binding protein (involved in local regulation of protein translation) in MB-V3 neurons impairs LTM. Our results suggest a model of long-term memory formation that includes a systems-level consolidation process, wherein an early, labile olfactory memory represented by neural activity in a sparse subset of MB neurons is converted into a stable LTM through protein synthesis in dendrites of MB-V3 neurons synapsed onto MB α lobes.L ong-term memory (LTM) and long-term synaptic plasticity require de novo protein synthesis, which is regulated at transcriptional and/or translational levels in a synapse-specific manner (1-3). Synapse-specific plasticity during LTM formation in some contexts may involve local regulation of protein translation by a family of RNA-binding proteins, the cytoplasmic polyadenylation element-binding proteins (CPEBs) (2). Neuronal CPEBs have two conformational states. The inactive state predominates at low levels of CPEB expression and represses translation from nascent mRNAs. The active state is achieved either via a self-perpetuating prion-like state when expression levels surpass a threshold or via Ca 2+ /calmoduline-dependent protein kinase II (CaMKII)-mediated phosphorylation, and translation is initiated by elongation of an mRNA's poly-A tail (4-6). In other species, CPEB1 has been shown to contribute to long-term facilitation or potentiation (5, 7). In Drosophila, oo18 RNA-binding protein 2 (ORB2) appears required for long-term memory formation after courtship conditioning (8, 9). Any role for ORB in fruit fly memory formation, however, remains unclear.Drosophila can learn to associate an odor (conditioned stimulus, CS) with foot-shock punishment (unconditioned stimulus, US). This odor-shock association initially is labile, lasting for only about a day after one training session. With repetitive, spaced training (ST) sessions (rest intervals between each session), a protein synthesis-dependent, LTM is formed. With repetitive, massed training (MT) ses...

Most animals exhibit innate auditory behaviors driven by genetically hardwired neural circuits. In Drosophila, acoustic information is relayed by Johnston organ neurons from the antenna to the antennal mechanosensory and motor center (AMMC) in the brain. Here, by using structural connectivity analysis, we identified five distinct types of auditory projection neurons (PNs) interconnecting the AMMC, inferior ventrolateral protocerebrum (IVLP), and ventrolateral protocerebrum (VLP) regions of the central brain. These auditory PNs are also functionally distinct; AMMC-B1a, AMMC-B1b, and AMMC-A2 neurons differ in their responses to sound (i.e., they are narrowly tuned or broadly tuned); one type of audioresponsive IVLP commissural PN connecting the two hemispheres is GABAergic; and one type of IVLP-VLP PN acts as a generalist responding to all tested audio frequencies. Our findings delineate an auditory processing pathway involving AMMC→IVLP→VLP in the Drosophila brain.calcium imaging | FlyCircuit | GFP reconstitution across synaptic partners | polarity A uditory systems are critical to the behavior of many insects. In Drosophila melanogaster, acoustic communication is essential for making decisions related to mate selection (1-4). During courtship, male flies flap one wing to produce a complex pattern of airborne vibrations comprising sine song and pulse song (5, 6). The pulse song enables the female to determine whether her suitor is of the same species (7). Courting males also monitor their own sounds to fine tune the courtship song (8). The courtship song is detected by auditory sensory neurons linking the Johnston organ (JO) at the second antennal segment to the antennal mechanosensory and motor center (AMMC) zones AB in the brain (9-12). It has been shown that the transient receptor potential vanilloid channels (Inactive and Nanchung) and a no mechanoreceptor potential C TRP channel expressed in JO-AB neurons are essential for normal acoustic transduction (13-16).Four different projection neurons (PNs) innervating the AMMC zones AB have been reported based on Gal4 expression patterns (12). The giant fiber neuron links AMMC zone A to the inferior ventrolateral protocerebrum (IVLP; a brain region defined by immunostaining of synaptic proteins) and thoracic ganglia; AMMC-A1 neuron connects AMMC zone A and the IVLP; AMMC-B1 neuron links AMMC zone B to the IVLP; and AMMC-B2 neurons are commissural neurons connecting AMMC zone B in both hemispheres. The intense innervations of the IVLP suggest that the IVLP functions as a second-level auditory processing center (12). More recently, stochastic labeling of 16,000 single neurons in the entire fly brain revealed that many AMMC PNs terminate at the caudoventrolateral protocerebrum (CVLP; a brain region analogous to IVLP and defined by clustered local neurons) (17), suggesting that the IVLP/CVLP region may be involved in auditory functions. However, a structural and functional map of cell-to-cell connectivity is first required to determine the direction of information flow,...

Although glucose-sensing neurons were discovered more than 50 years ago, the physiological role of glucose sensing in metazoans remains unclear. Here, we identify a pair of glucose-sensing neurons (dubbed CN neurons) in the Drosophila brain with bifurcating axons whereby one axon branch projects to insulin-producing cells (IPCs) to trigger the release of Drosophila insulin-like peptide 2 (dilp2), and the other one extends to adipokinetic hormone (AKH)-producing cells to inhibit the secretion of AKH, fly's analog of glucagon. These axonal branches undergo synaptic remodeling in response to changes in their internal energy status. Silencing of CN neurons largely disabled IPCs' response to glucose and dilp2 secretion, and disinhibited AKH secretion in corpora cardiaca (CC), and caused hyperglycemia, a hallmark feature of diabetes mellitus. We propose that CN neurons maintain glucose homeostasis by promoting the secretion of dilp2 and suppressing the release of AKH when hemolymph glucose levels are high.Glucose-sensing neurons respond to glucose or its metabolite that act as a signaling cue to regulate their neuronal activity. According to the glucostatic hypothesis proposed in 1953, Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Gap junctions play an important role in the regulation of neuronal metabolism and homeostasis by serving as connections that enable small molecules to pass between cells and synchronize activity between cells. Although recent studies have linked gap junctions to memory formation, it remains unclear how they contribute to this process. Gap junctions are hexameric hemichannels formed from the connexin and pannexin gene families in chordates and the innexin (inx) gene family in invertebrates. Here we show that two modulatory neurons, the anterior paired lateral (APL) neuron and the dorsal paired medial (DPM) neuron, form heterotypic gap junctions within the mushroom body (MB), a learning and memory center in the Drosophila brain. Using RNA interference-mediated knockdowns of inx7 and inx6 in the APL and DPM neurons, respectively, we found that flies showed normal olfactory associative learning and intact anesthesia-resistant memory (ARM) but failed to form anesthesia-sensitive memory (ASM). Our results reveal that the heterotypic gap junctions between the APL and DPM neurons are an essential part of the MB circuitry for memory formation, potentially constituting a recurrent neural network to stabilize ASM.