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Connectomes generated from electron microscopy images of neural tissue unveil the complex morphology of every neuron and the locations of every synapse interconnecting them. These wiring diagrams may also enable inference of synaptic and neuronal biophysics, such as the functional weights of synaptic connections, but this requires integration with physiological data to properly parameterize. Working with a stereotyped olfactory network in the Drosophila brain, we make direct comparisons of the anatomy and physiology of diverse neurons and synapses with subcellular and subthreshold resolution. We find that synapse density and location jointly predict the amplitude of the somatic postsynaptic potential evoked by a single presynaptic spike. Biophysical models fit to data predict that electrical compartmentalization allows axon and dendrite arbors to balance independent and interacting computations. These findings begin to fill the gap between connectivity maps and activity maps, which should enable new hypotheses about how network structure constrains network function., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Three new studies use a whole adult brain electron microscopy volume to reveal new long-range connectivity maps of complete populations of neurons in olfactory, thermosensory, hygrosensory, and memory systems in the fly Drosophila melanogaster., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Broad neuronal classes are surprisingly heterogeneous across many parameters, and subclasses often exhibit partially overlapping traits including transmitter coexpression. However, the extent to which transmitter coexpression occurs in predictable, consistent patterns is unknown. Here, we demonstrate that pairwise coexpression of GABA and multiple neuropeptide families by olfactory local interneurons (LNs) of the moth Manduca sexta is highly heterogeneous, with a single LN capable of expressing neuropeptides from at least four peptide families and few instances in which neuropeptides are consistently coexpressed. Using computational modeling, we demonstrate that observed coexpression patterns cannot be explained by independent probabilities of expression of each neuropeptide. Our analyses point to three organizing principles that, once taken into consideration, allow replication of overall coexpression structure: (1) peptidergic neurons are highly likely to coexpress GABA; (2) expression probability of allatotropin depends on myoinhibitory peptide expression; and (3) the all-or-none coexpression patterns of tachykinin neurons with several other neuropeptides. For other peptide pairs, the presence of one peptide was not predictive of the presence of the other, and coexpression probability could be replicated by independent probabilities. The stochastic nature of these coexpression patterns highlights the heterogeneity of transmitter content among LNs and argues against clear-cut definition of subpopulation types based on the presence of single neuropeptides. Furthermore, the receptors for all neuropeptides and GABA were expressed within each population of principal neuron type in the antennal lobe (AL). Thus, activation of any given LN results in a dynamic cocktail of modulators that have the potential to influence every level of olfactory processing within the AL.

Neuromodulation is a ubiquitous feature of neural systems, allowing flexible, context specific control over network dynamics. Neuromodulation was first described in invertebrate motor systems and early work established a basic dichotomy for neuromodulation as having either an intrinsic origin (i.e., neurons that participate in network coding) or an extrinsic origin (i.e., neurons from independent networks). In this conceptual dichotomy, intrinsic sources of neuromodulation provide a "memory" by adjusting network dynamics based upon previous and ongoing activation of the network itself, while extrinsic neuromodulators provide the context of ongoing activity of other neural networks. Although this dichotomy has been thoroughly considered in motor systems, it has received far less attention in sensory systems. In this review, we discuss intrinsic and extrinsic modulation in the context of olfactory processing in invertebrate and vertebrate model systems. We begin by discussing presynaptic modulation of olfactory sensory neurons by local interneurons (LNs) as a mechanism for gain control based on ongoing network activation. We then discuss the cell-class specific effects of serotonergic centrifugal neurons on olfactory processing. Finally, we briefly discuss the integration of intrinsic and extrinsic neuromodulation (metamodulation) as an effective mechanism for exerting global control over olfactory network dynamics. The heterogeneous nature of neuromodulation is a recurring theme throughout this review as the effects of both intrinsic and extrinsic modulation are generally non-uniform.

The release of neuromodulators by widely projecting neurons often allows sensory systems to alter how they process information based on the physiological state of an animal. Neuromodulators alter network function by changing the biophysical properties of individual neurons and the synaptic efficacy with which individual neurons communicate. However, most, if not all, sensory networks receive multiple neuromodulatory inputs, and the mechanisms by which sensory networks integrate multiple modulatory inputs are not well understood. Here we characterized the relative glomerular distribution of two extrinsic neuromodulators associated with distinct physiological states, serotonin (5-HT) and dopamine (DA), in the antennal lobe (AL) of the moth Manduca sexta. By using immunocytochemistry and mass dye fills, we characterized the innervation patterns of both 5-HT- and tyrosine hydroxylase-immunoreactive processes relative to each other, to olfactory receptor neurons (ORNs), to projection neurons (PNs), and to several subsets of local interneurons (LNs). 5-HT immunoreactivity had nearly complete overlap with PNs and LNs, yet no overlap with ORNs, suggesting that 5-HT may modulate PNs and LNs directly but not ORNs. TH immunoreactivity overlapped with PNs, LNs, and ORNs, suggesting that dopamine has the potential to modulate all three cell types. Furthermore, the branching density of each neuromodulator differed, with 5-HT exhibiting denser arborizations and TH-ir processes being sparser. Our results suggest that 5-HT and DA extrinsic neurons target partially overlapping glomerular regions, yet DA extends further into the region occupied by ORNs., (© 2015 Wiley Periodicals, Inc.)

Neural circuits projecting information from motor to sensory pathways are common across sensory domains. These circuits typically modify sensory function as a result of motor pattern activation; this is particularly so in cases where the resultant behavior affects the sensory experience or its processing. However, such circuits have not been observed projecting to an olfactory pathway in any species despite well characterized active sampling behaviors that produce reafferent mechanical stimuli, such as sniffing in mammals and wing beating in the moth Manduca sexta. In this study we characterize a circuit that connects a flight sensory-motor center to an olfactory center in Manduca. This circuit consists of a single pair of histamine immunoreactive (HA-ir) neurons that project from the mesothoracic ganglion to innervate a subset of ventral antennal lobe (AL) glomeruli. Furthermore, within the AL we show that the M. sexta histamine B receptor (MsHisClB) is exclusively expressed by a subset of GABAergic and peptidergic LNs, which broadly project to all olfactory glomeruli. Finally, the HA-ir cell pair is present in fifth stage instar larvae; however, the absence of MsHisClB-ir in the larval antennal center indicates that the circuit is incomplete prior to metamorphosis and importantly prior to the expression of flight behavior. Although the functional consequences of this circuit remain unknown, these results provide the first detailed description of a circuit that interconnects an olfactory system with motor centers driving flight behaviors including odor-guided flight.