The wiring logic of an identified serotonergic neuron that spans sensory networks

Abstract

19Serotonergic neurons modulate diverse physiological and behavioral processes in a 20 context-dependent manner, based on their complex connectivity. However, their 21 connectivity has not been comprehensively explored at a single-cell resolution. Using a 22 whole-brain EM dataset we determined the wiring logic of a broadly projecting 23 serotonergic neuron (the "CSDn") in Drosophila. Within the antennal lobe (AL; first-order 24 olfactory region), the CSDn receives glomerulus-specific input and preferentially targets 25 distinct local interneuron subtypes. Furthermore, the wiring logic of the CSDn differs 26 between olfactory regions. The CSDn innervates the AL and lateral horn (LH), yet does 27 not maintain the same synaptic relationship with individual projection neurons that also 28 span both regions. Consistent with this, the CSDn has more distributed connectivity in 29 the LH relative to the AL, preferentially synapsing with principal neuron types based on 30 presumptive transmitter content. Lastly, we identify protocerebral neurons that provide 31 abundant synaptic input to the CSDn. Our study demonstrates how an individual 32 modulatory neuron can interact with local networks and integrate input from non-33 olfactory sources. 35Introduction 36 Every neural network receives modulatory input from a variety of sources [1, 2], 37 and in some cases from heterogeneous populations of neurons that release the same 38 modulatory transmitter [3][4][5]. In mammals, one ubiquitous neuromodulator, serotonin, is 39 released by tens of thousands to hundreds of thousands of neurons which originate in 40 the raphe nuclei and project throughout the brain [6, 7]. Serotonergic raphe neurons are 41 highly diverse in their projections, connectivity, and electrophysiological properties, and 42 2 are implicated in a wide breadth of behaviors and physiological processes [4,[8][9][10][11][12][13][14][15][16]. 43 Further, the raphe system receives monosynaptic input from up to 80 anatomical areas 44 [8, 9]. As a result, a significant amount of work has focused on disentangling the 45 functional and behavioral roles of serotonergic neurons. Several recent studies have 46 suggested that serotonergic raphe neurons may be organized into functional 47 subpopulations based on neuroanatomy, electrophysiology, and behavior [4, 12,[17][18][19][20][21]. 48For example, two parallel sub-systems of serotonergic raphe neurons collateralize 49 complimentarily and are both activated by reward, yet have opposing responses to 50 aversive stimuli and promote distinct behaviors [18]. Sparse neuron reconstructions in 51 mice show that a single serotonin neuron can interconnect the olfactory bulb, piriform 52 cortex, and anterior olfactory nucleus [19], demonstrating that a single serotonergic 53 neuron can arborize several processing stages within the same sensory modality. Thus, 54 determining the precise patterns of connectivity of single serotonergic neurons within 55 and across the brain regions will be critical for understanding t...

Complete Connectomic Reconstruction of Olfactory Projection Neurons in the Fly Brain

“…For this, we chose multiple cross sections through the base of each tract and reconstructed all neurons within it to identification. For completeness, we note the serotonergic CSD neuron which we excluded from our list because its unpolarised nature precludes it from being classified as a classical projection neuron [72,88,89].…”

“…Neuronal reconstruction for this project took place in a collaborative CATMAID environment in which 27 labs are participating to build connectomes for specific circuits. Therefore, work done for published (Dolan et al[14,15], Zheng et al[21], Sayin et al[80], and Coates et al[72]) and ongoing projects has proved useful to us. We thank Fiona Love, Billy Morris, Amelia Edmondson-Stait, Kimberly Meechan, Jawaid Ali, Clement Hallou, Mahmoud Elbahnasawi, Lucia Kmecova, Paavo Huoviala, Zane Mitrevica, Nadiya Sharifi, Istvá n Taisz, Irene Varela, Najla Masoodpanah, Melissa Ryan, Peter Gibb, Kaylynn Coates, Shanice Bailey, Quinn Vanderbeck, Jason Polsky, Joseph Hsu, Benjamin Gorko, Jacob Ratliff, Michael Lingelbach, Aidan Smith, Amalia Braun, Adam Heath, Corey Fisher, Kathi Eichler, Ben Koppenhaver, Jeremy Johnson, Przemyslaw Jarzebowski, Remy Tabano, Claire Managan, Johann Schor, Katie Stevens, Adam John, Shada Alghailani, Lindsey Tagg, (C) Diagram of the MB lobes, colored by putative valence[3,11].…”