A Neural Circuit Arbitrates between Persistence and Withdrawal in Hungry Drosophila

Sayın, Sercan; Backer, Jean-François De; Siju, K.P.; Wosniack, Marina E.; Lewis, Laurence; Frisch, Lisa M.; Gansen, Benedikt; Schlegel, Philipp; Edmondson-Stait, Amelia J.; Sharifi, Nadiya; Fisher, Corey B.; Calle-Schuler, Steven A.; Lauritzen, J. Scott; Bock, Davi D.; Costa, Marta; Jefferis, Gregory; Gjorgjieva, Julijana; Kadow, Ilona C. Grunwald

doi:10.1016/j.neuron.2019.07.028

Cited by 110 publications

(124 citation statements)

References 80 publications

(144 reference statements)

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“…Neuronal reconstruction for this project took place in a collaborative CATMAID environment, in which in which 27 labs are participating to build draft connectomes for specific circuits. As a consequence, work done for other published (Dolan et al [13,15], Zheng et al [21], and Sayin et al [72]) and ongoing projects has also proved useful to us. We thank Fiona Love, Billy Morris, Amelia Edmondson-Stait, Laia Ser- Theiss for together contributing~30% of the novel neuronal cable used in this study manuscript.…”

Section: Acknowledgementsmentioning

confidence: 86%

Complete connectomic reconstruction of olfactory projection neurons in the fly brain

Bates

Schlegel

Roberts

et al. 2020

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Nervous systems contain sensory neurons, local neurons, projection neurons and motor neurons. To understand how these building blocks form whole circuits, we must distil these broad classes into neuronal cell types and describe their network connectivity. Using an electron micrograph dataset for an entire Drosophila melanogaster brain, we reconstruct the first complete inventory of olfactory projections connecting the antennal lobe, the insect analogue of the mammalian olfactory bulb, to higher-order brain regions in an adult animal brain. We then connect this inventory to extant data in the literature, providing synaptic-resolution 'holotypes' both for heavily investigated and previously unknown cell types. Projection neurons are approximately twice as numerous as reported by light level studies; cell types are stereotyped, but not identical, in cell and synapse numbers between brain hemispheres. The lateral horn, the insect analogue of the mammalian cortical amygdala, is the main target for this olfactory information and has been shown to guide innate behaviour. Here, we find new connectivity motifs, including: axo-axonic connectivity between projection neurons; feedback and lateral inhibition of these axons by local neurons; and the convergence of different inputs, including non-olfactory inputs and memory-related feedback onto lateral horn neurons. This differs from the configuration of the second most prominent target for olfactory projection neurons: the mushroom body calyx, the insect analogue of the mammalian piriform cortex and a centre for associative memory. Our work provides a complete neuroanatomical platform for future studies of the adult Drosophila olfactory system. Highlights• First complete parts list for second-order neurons of an adult olfactory system • Quantification of left-right stereotypy in cell and synapse number • Axo-axonic connections form hierarchical communities in the lateral horn • Local neurons and memory-related feedback target projection neuron axons 149 197 346 Figure 1: Second-order olfactory projection neurons. A Layout of the mammalian olfactory system. B The olfactory system in fruit flies shares similarities with that of mammals. C Second-order olfactory projection neurons (PNs) in all antennal lobe tracts (ALT) were reconstructed from a serial section transmission electron microscopy (ssTEM) volume of an entire fly brain. Scale bar represents 1 micron. D Exemplary sparse (left) and broad (right) PN. Dendrites used for classification in blue. E PNs were classified as uni-(uPN) or multiglomerular (mPN) projection neurons based on the sparseness of their glomerular innervation (see also Figure S1). F PN counts by class and neurotransmitter. G Comparison of right-(RHS) vs left-hand-side (LHS) cell counts for 58 of the 78 uPN types. H Scaling of the olfactory system from larval to adult D. melanogaster. Bates, Schlegel et al. 2 / 31

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Section: Acknowledgementsmentioning

confidence: 86%

Complete connectomic reconstruction of olfactory projection neurons in the fly brain

Bates

Schlegel

Roberts

et al. 2020

Preprint

218

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“…6A) that has a long vertical medial projection (see also (Wu et al, 2019). We manually detected all synaptic connections, as done previously Sayin et al, 2019;Zheng et al, 2018). After excluding very weak connections (using 3 synapses as a threshold, see Methods), we counted 417 presynaptic and 421 postsynaptic sites ( Fig.…”

Section: Pc1-alpha Is Reciprocally Connected To a Specific Subset Ofmentioning

confidence: 99%

“…Internal brain states influence perceptions, decision-making, and actions (Anderson, 2016;Berridge, 2004;Lorenz and Leyhausen, 1973) -for example, when hungry, we make different decisions about what to do (prioritizing searching out food over other tasks) and what to eat (expanding the repertoire of foods we find appetizing) based on our hunger status (Sayin et al, 2019;Sternson et al, 2013). The timescales of persistence of an internal brain state can varysome, like sleep-wake cycles, persist over hours (Scammell et al, 2017;Shaw et al, 2000), while others may last only a few seconds (Calhoun et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

The Neural Basis for a Persistent Internal State inDrosophilaFemales

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Encarnacion-Rivera

et al. 2020

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Sustained changes in mood or action require persistent changes in neural activity, but it has been difficult to identify and characterize the neural circuit mechanisms that underlie persistent activity and contribute to long-lasting changes in behavior. Here, we focus on changes in the behavioral state of Drosophila females that persist for minutes following optogenetic activation of a single class of central brain neurons termed pC1. We find that female pC1 neurons drive a variety of persistent behaviors in the presence of males, including increased receptivity, shoving, and chasing. By reconstructing cells in a volume electron microscopic image of the female brain, we classify 7 different pC1 cell types and, using cell type specific driver lines, determine that one of these, pC1-Alpha, is responsible for driving persistent female shoving and chasing. Using calcium imaging, we locate sites of minutes-long persistent neural activity in the brain, which include pC1 neurons themselves. Finally, we exhaustively reconstruct all synaptic partners of a single pC1-Alpha neuron, and find recurrent connectivity that could support the persistent neural activity. Our work thus links minutes-long persistent changes in behavior with persistent neural activity and recurrent circuit architecture in the female brain.

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“…Does this range encompass functional connections? While there is no single answer for how many synapses constitute a ‘functional connection’, recent work has found that seemingly low connection strengths, in the region of rv2% of a neuron’s total post-synaptic budget, can be functional [12, 16, 38, 48]. In the case of PD2a1/b1 and AV1a1neurons used in this study, the average number of post-synapses per neuron is 673, implying a 2% threshold value of around 12 synapses (Table S16).…”

Section: Discussionmentioning

confidence: 99%

BAcTrace a new tool for retrograde tracing of neuronal circuits

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Gkantia

Bates

et al. 2020

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11New tools and techniques have enabled many key advances in our understanding of the brain. To elucidate circuit function, it is necessary to identify, record from and manipulate networks of connected neurons. Here we present BAcTrace (Botulinum Activated Tracer), the first fully genetically encoded, retrograde, transsynaptic labelling system. BAcTrace is based on C. botulinum neurotoxin A, Botox, which we have engineered to act as a Trojan horse that jumps retrogradely between neurons to activate an otherwise silent transcription factor. We validate BAcTrace at three connections in the Drosophila olfactory system and show that it enables electrophysiological recordings of connected neurons. Finally, in a challenging circuit with highly divergent connections, we used Electron Microscopy connectomics to show that BAcTrace correctly identifies 12 out of 16 connections.The development of genetic tools to elucidate connectivity and manipulate neurons and circuits has 13 been key to advancing our understanding of how the brain works. Increasingly these tools are being 14 used to study diseases of the nervous system and develop effective treatments [31, 57]. 15In the context of circuit research, the ability to identify and manipulate pre-or post-synaptic cells to 16 neurons of interest is of crucial importance. For example, if genetic drivers are available for sensory 17 neurons in the skin then one might want to label downstream, post-synaptic cells in the nerve cord. 18Conversely, when studying motor circuits, genetic drivers for motor neurons might be available and 19 revealing upstream, pre-synaptic cells will be appropriate. Tools to label downstream neurons (e.g. for 20 "walking" from sensory input towards motor-outputs as in the first example) are called anterograde, 21 while retrograde tools reveal the input neurons to a given population. 22Drosophila melanogaster is a key model organisms to study the genetic and circuit basis of animal 23 behaviour (e.g. see [62, 15]). The fly has a rich behavioural repertoire encoded in a relatively small 24 nervous system. This numerical simplicity is paired with extensive collections of genetic reagents, 25 both to investigate gene function (e.g. mutant and RNAi collections) and to label and manipulate 26 most neuronal classes (using the orthogonal expression systems Gal4, LexA, QF and their split versions 27 [4, 45, 30, 58]). While these reagents offer excellent genetic access to neurons, until recently the 28 fly lacked tools to map synaptic connections between neurons. This has recently changed with the 29 development of electron microscopy methods to map connections in larval [38] and adult [63] brains. 30 Furthermore, two genetically encoded systems for anterograde tracing: trans-Tango [54] and TRACT 31 [22] have recently been developed. Despite these important additions to the experimental toolbox, a 32 retrograde labelling system is still missing. Rabies virus and its modifications constitute the most notable 33 examples of retrograde transsynaptic tools [31]. While...

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A Neural Circuit Arbitrates between Persistence and Withdrawal in Hungry Drosophila

Cited by 110 publications

References 80 publications

Complete connectomic reconstruction of olfactory projection neurons in the fly brain

Complete connectomic reconstruction of olfactory projection neurons in the fly brain

The Neural Basis for a Persistent Internal State inDrosophilaFemales

BAcTrace a new tool for retrograde tracing of neuronal circuits

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