scholarly journals Complete connectomic reconstruction of olfactory projection neurons in the fly brain

2020 ◽  
Author(s):  
A.S. Bates ◽  
P. Schlegel ◽  
R.J.V. Roberts ◽  
N. Drummond ◽  
I.F.M. Tamimi ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Olfactory System ◽  
Neuronal Cell ◽  
Building Blocks ◽  
Cell Types ◽  
Projection Neuron ◽  
Brain Regions ◽  
Projection Neurons ◽  
List Type ◽  
Lateral Horn

AbstractNervous 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.HighlightsFirst complete parts list for second-order neurons of an adult olfactory systemQuantification of left-right stereotypy in cell and synapse numberAxo-axonic connections form hierarchical communities in the lateral hornLocal neurons and memory-related feedback target projection neuron axons

scholarly journals Functional and anatomical specificity in a higher olfactory centre

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Shahar Frechter ◽  
Alexander Shakeel Bates ◽  
Sina Tootoonian ◽  
Michael-John Dolan ◽  
James Manton ◽  
...  
Keyword(s):  
Olfactory System ◽  
Mushroom Body ◽  
Cell Types ◽  
Sensory Systems ◽  
Projection Neurons ◽  
Olfactory Behavior ◽  
Population Code ◽  
Odor Coding ◽  
Sensory Stimuli ◽  
Lateral Horn

Most sensory systems are organized into parallel neuronal pathways that process distinct aspects of incoming stimuli. In the insect olfactory system, second order projection neurons target both the mushroom body, required for learning, and the lateral horn (LH), proposed to mediate innate olfactory behavior. Mushroom body neurons form a sparse olfactory population code, which is not stereotyped across animals. In contrast, odor coding in the LH remains poorly understood. We combine genetic driver lines, anatomical and functional criteria to show that the Drosophila LH has ~1400 neurons and >165 cell types. Genetically labeled LHNs have stereotyped odor responses across animals and on average respond to three times more odors than single projection neurons. LHNs are better odor categorizers than projection neurons, likely due to stereotyped pooling of related inputs. Our results reveal some of the principles by which a higher processing area can extract innate behavioral significance from sensory stimuli.

scholarly journals A novel population of long-range inhibitory neurons

2019 ◽  
Author(s):  
Zoé Christenson Wick ◽  
Madison R. Tetzlaff ◽  
Esther Krook-Magnuson
Keyword(s):  
Long Range ◽  
Viral Vector ◽  
Neuronal Cell ◽  
Building Blocks ◽  
Cell Types ◽  
Neuronal Population ◽  
Inhibitory Neurons ◽  
Projection Neurons ◽  
Neuronal Diversity ◽  
Rich Diversity

AbstractThe hippocampus, a brain region important for spatial navigation and episodic memory, benefits from a rich diversity of neuronal cell-types. Recent work suggests fundamental gaps in our knowledge of these basic building blocks (i.e., neuronal types) in the hippocampal circuit, despite extensive prior examination. Through the use of an intersectional genetic viral vector approach, we report a novel hippocampal neuronal population, which has not previously been characterized, and which we refer to as LINCs. LINCs are GABAergic, but, in addition to broadly targeting local CA1 cells, also have long-range axons. LINCs are thus both interneurons and projection neurons. We demonstrate that LINCs, despite being relatively few in number, can have a strong influence on both hippocampal and extrahippocampal network synchrony and function. Identification and characterization of this novel cell population advances our basic understanding of both hippocampal circuitry and neuronal diversity.

scholarly journals Olfactory processing in the lateral horn of Drosophila

2021 ◽  
Vol 383 (1) ◽  
pp. 113-123
Author(s):  
Sudeshna Das Chakraborty ◽  
Silke Sachse
Keyword(s):  
Functional Properties ◽  
Olfactory System ◽  
Cell Types ◽  
Specific Cell ◽  
Olfactory Behavior ◽  
Lateral Horn ◽  
Behavioral Decision ◽  
Animal Phyla ◽  
Survival And Reproduction ◽  
Almost All

AbstractSensing olfactory signals in the environment represents a crucial and significant task of sensory systems in almost all organisms to facilitate survival and reproduction. Notably, the olfactory system of diverse animal phyla shares astonishingly many fundamental principles with regard to anatomical and functional properties. Binding of odor ligands by chemosensory receptors present in the olfactory peripheral organs leads to a neuronal activity that is conveyed to first and higher-order brain centers leading to a subsequent odor-guided behavioral decision. One of the key centers for integrating and processing innate olfactory behavior is the lateral horn (LH) of the protocerebrum in insects. In recent years the LH of Drosophila has garnered increasing attention and many studies have been dedicated to elucidate its circuitry. In this review we will summarize the recent advances in mapping and characterizing LH-specific cell types, their functional properties with respect to odor tuning, their neurotransmitter profiles, their connectivity to pre-synaptic and post-synaptic partner neurons as well as their impact for olfactory behavior as known so far.

scholarly journals Prevalent presence of periodic actin–spectrin-based membrane skeleton in a broad range of neuronal cell types and animal species

2016 ◽  
Vol 113 (21) ◽  
pp. 6029-6034 ◽  
Author(s):  
Jiang He ◽  
Ruobo Zhou ◽  
Zhuhao Wu ◽  
Monica A. Carrasco ◽  
Peri T. Kurshan ◽  
...  
Keyword(s):  
Glial Cell ◽  
Animal Species ◽  
Homo Sapiens ◽  
Neuronal Cell ◽  
Cell Types ◽  
Membrane Skeleton ◽  
Brain Regions ◽  
Inhibitory Neurons ◽  
Periodic Distribution ◽  
Neuronal Types

Actin, spectrin, and associated molecules form a periodic, submembrane cytoskeleton in the axons of neurons. For a better understanding of this membrane-associated periodic skeleton (MPS), it is important to address how prevalent this structure is in different neuronal types, different subcellular compartments, and across different animal species. Here, we investigated the organization of spectrin in a variety of neuronal- and glial-cell types. We observed the presence of MPS in all of the tested neuronal types cultured from mouse central and peripheral nervous systems, including excitatory and inhibitory neurons from several brain regions, as well as sensory and motor neurons. Quantitative analyses show that MPS is preferentially formed in axons in all neuronal types tested here: Spectrin shows a long-range, periodic distribution throughout all axons but appears periodic only in a small fraction of dendrites, typically in the form of isolated patches in subregions of these dendrites. As in dendrites, we also observed patches of periodic spectrin structures in a small fraction of glial-cell processes in four types of glial cells cultured from rodent tissues. Interestingly, despite its strong presence in the axonal shaft, MPS is disrupted in most presynaptic boutons but is present in an appreciable fraction of dendritic spine necks, including some projecting from dendrites where such a periodic structure is not observed in the shaft. Finally, we found that spectrin is capable of adopting a similar periodic organization in neurons of a variety of animal species, including Caenorhabditis elegans, Drosophila, Gallus gallus, Mus musculus, and Homo sapiens.

scholarly journals Classifying Drosophila Olfactory Projection Neuron Subtypes by Single-cell RNA Sequencing

2017 ◽  
Author(s):  
Hongjie Li ◽  
Felix Horns ◽  
Bing Wu ◽  
Qijing Xie ◽  
Jiefu Li ◽  
...  
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Neuronal Cell ◽  
Projection Neuron ◽  
Projection Neurons ◽  
Open Questions ◽  
Olfactory Glomeruli ◽  
Single Cell Rna Sequencing ◽  
Genes Encoding ◽  
Circuit Assembly

AbstractHow a neuronal cell type is defined and how this relates to its transcriptome are still open questions. The Drosophila olfactory projection neurons (PNs) are among the best-characterized neuronal types: Different PN classes target dendrites to distinct olfactory glomeruli and PNs of the same class exhibit indistinguishable anatomical and physiological properties. Using single-cell RNA-sequencing, we comprehensively characterized the transcriptomes of 40 PN classes and unequivocally identified transcriptomes for 6 classes. We found a new lineage-specific transcription factor that instructs PN dendrite targeting. Transcriptomes of closely-related PN classes exhibit the largest difference during circuit assembly, but become indistinguishable in adults, suggesting that neuronal subtype diversity peaks during development. Genes encoding transcription factors and cell-surface molecules are the most differentially expressed, indicating their central roles in specifying neuronal identity. Finally, we show that PNs use highly redundant combinatorial molecular codes to distinguish subtypes, enabling robust specification of cell identity and circuit assembly.

scholarly journals Distinct properties in ventral pallidum projection neuron subtypes

2021 ◽  
Author(s):  
Nimrod Bernat ◽  
Rianne Campbell ◽  
Hyungwoo Nam ◽  
Mahashweta Basu ◽  
Tal Odesser ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Critical Role ◽  
Gene Expression Profiles ◽  
Cell Types ◽  
Projection Neuron ◽  
Brain Regions ◽  
Ventral Pallidum ◽  
Lateral Habenula

The ventral pallidum (VP), a major component of the basal ganglia, plays a critical role in motivational disorders. It sends projections to many different brain regions but it is not yet known whether and how these projections differ in their cellular properties, gene expression patterns, connectivity and role in reward seeking. In this study, we focus on four major outputs of the VP - to the lateral hypothalamus (LH), ventral tegmental area (VTA), mediodorsal thalamus (MDT), and lateral habenula (LHb) - and examine the differences between them in 1) baseline gene expression profiles using projection-specific RNA-sequencing; 2) physiological parameters using whole-cell patch clamp; and 3) their influence on cocaine reward using chemogenetic tools. We show that these four VP efferents differ in all three aspects and highlight specifically differences between the projections to the LH and the VTA. These two projections originate largely from separate populations of neurons, express distinct sets of genes related to neurobiological functions, and show opposite physiological and behavioral properties. Collectively, our data demonstrates for the first time that VP neurons exhibit distinct molecular and cellular profiles in a projection-specific manner, suggesting that they represent different cell types.

scholarly journals Information flow, cell types and stereotypy in a full olfactory connectome

2020 ◽  
Author(s):  
Philipp Schlegel ◽  
Alexander Shakeel Bates ◽  
Tomke Stürner ◽  
Sridhar R. Jagannathan ◽  
Nikolas Drummond ◽  
...  
Keyword(s):  
Information Flow ◽  
Olfactory System ◽  
Mushroom Body ◽  
Antennal Lobe ◽  
Large Scale ◽  
Cell Types ◽  
Neuronal Morphology ◽  
Striking Similarity ◽  
Data Set ◽  
Lateral Horn

AbstractThe hemibrain connectome (Scheffer et al., 2020) provides large scale connectivity and morphology information for the majority of the central brain of Drosophila melanogaster. Using this data set, we provide a complete description of the most complex olfactory system studied at synaptic resolution to date, covering all first, second and third-order neurons of the olfactory system associated with the antennal lobe and lateral horn (mushroom body neurons are described in a parallel paper, (Li et al., 2020)). We develop a generally applicable strategy to extract information flow and layered organisation from synaptic resolution connectome graphs, mapping olfactory input to descending interneurons. This identifies a range of motifs including highly lateralised circuits in the antennal lobe and patterns of convergence downstream of the mushroom body and lateral horn. We also leverage a second data set (FAFB, (Zheng et al., 2018)) to provide a first quantitative assessment of inter- versus intra-individual stereotypy. Complete reconstruction of select developmental lineages in two brains (three brain hemispheres) reveals striking similarity in neuronal morphology across brains for >170 cell types. Within and across brains, connectivity correlates with morphology. Notably, neurons of the same morphological type show similar connection variability within one brain as across brains; this property should enable a rigorous quantitative approach to cell typing.

scholarly journals Chemogenetic restoration of autonomous subthalamic nucleus activity ameliorates Parkinsonian motor dysfunction

2018 ◽  
Author(s):  
Eileen L. McIver ◽  
Hong-Yuan Chu ◽  
Jeremy F. Atherton ◽  
Kathleen E. Cosgrove ◽  
Jyothisri Kondapalli ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Subthalamic Nucleus ◽  
Projection Neuron ◽  
Motor Dysfunction ◽  
Projection Neurons ◽  
List Type ◽  
Oxygen Species ◽  
Striatal Projection Neurons ◽  
Autonomous Activity ◽  
Genetic Mouse Models

Highlightsdecorrelating autonomous STN activity was downregulated in both toxin and genetic models of PDelevation of D2-striatal projection neuron transmission was sufficient for downregulationdownregulation was dependent on activation of STN NMDA receptors and KATP channelschemogenetic restoration of autonomous spiking reduced synaptic patterning of STN neurons and PD motor dysfunctioneToCExcessive synaptic synchronization of STN activity is linked to the symptomatic expression of PD.McIver and colleagues describe the cellular and circuit mechanisms responsible for the loss of decorrelating autonomous STN activity in PD models and demonstrate that chemogenetic rescue of autonomous spiking reduces synaptically patterned STN activity and ameliorates Parkinsonian motor dysfunction.SUMMARYExcessive, synaptically-driven synchronization of subthalamic nucleus (STN) neurons is widely thought to contribute to akinesia, bradykinesia, and rigidity in Parkinson’s disease (PD). Electrophysiological, optogenetic, chemogenetic, genetic, 2-photon imaging, and pharmacological approaches revealed that the autonomous activity of STN neurons, which opposes synaptic synchronization, was downregulated in both toxin and genetic mouse models of PD.Loss of autonomous spiking was due to increased transmission of D2-striatal projection neurons, leading in the STN to elevated activation of NMDA receptors and generation of reactive oxygen species that promoted KATP channel opening.Chemogenetic restoration of autonomous firing in STN neurons reduced synaptic patterning and ameliorated Parkinsonian motor dysfunction, arguing that elevating intrinsic STN activity is an effective therapeutic intervention in PD.

scholarly journals Reconstruction of 1,000 projection neurons reveals new cell types and organization of long-range connectivity in the mouse brain

2019 ◽  
Author(s):  
Johan Winnubst ◽  
Erhan Bas ◽  
Tiago A. Ferreira ◽  
Zhuhao Wu ◽  
Michael N. Economo ◽  
...  
Keyword(s):  
Long Range ◽  
Mouse Brain ◽  
Neuronal Cell ◽  
Cell Types ◽  
Neuronal Morphology ◽  
Projection Neurons ◽  
Axonal Arbor ◽  
Flow Of Information ◽  
Organizational Principles ◽  
The Brain

SummaryNeuronal cell types are the nodes of neural circuits that determine the flow of information within the brain. Neuronal morphology, especially the shape of the axonal arbor, provides an essential descriptor of cell type and reveals how individual neurons route their output across the brain. Despite the importance of morphology, few projection neurons in the mouse brain have been reconstructed in their entirety. Here we present a robust and efficient platform for imaging and reconstructing complete neuronal morphologies, including axonal arbors that span substantial portions of the brain. We used this platform to reconstruct more than 1,000 projection neurons in the motor cortex, thalamus, subiculum, and hypothalamus. Together, the reconstructed neurons comprise more than 75 meters of axonal length and are available in a searchable online database. Axonal shapes revealed previously unknown subtypes of projection neurons and suggest organizational principles of long-range connectivity.

scholarly journals Differential encoding in prefrontal cortex projection neuron classes across cognitive tasks

2020 ◽  
Author(s):  
Jan H. Lui ◽  
Nghia D. Nguyen ◽  
Sophie M. Grutzner ◽  
Spyros Darmanis ◽  
Diogo Peixoto ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Cortical Neurons ◽  
Cell Types ◽  
Projection Neuron ◽  
Cognitive Tasks ◽  
Mammalian Brain ◽  
Projection Neurons ◽  
Differential Encoding ◽  
Alternative Choice ◽  
Choice Tasks

SUMMARYSingle-cell transcriptomics has been widely applied to classify neurons in the mammalian brain, while systems neuroscience has historically analyzed the encoding properties of cortical neurons without considering cell types. Here we examine how specific transcriptomic types of mouse prefrontal cortex (PFC) projection neurons relate to axonal projections and encoding properties across multiple cognitive tasks. We found that most types projected to multiple targets, and most targets received projections from multiple types, except PFC→PAG (periaqueductal gray). By comparing Ca2+-activity of the molecularly homogeneous PFC→PAG type against two heterogeneous classes in several two-alternative choice tasks in freely-moving mice, we found that all task-related signals assayed were qualitatively present in all examined classes. However, PAG-projecting neurons most potently encoded choice in cued tasks, whereas contralateral PFC-projecting neurons most potently encoded reward context in an uncued task. Thus, task signals are organized redundantly, but with clear quantitative biases across cells of specific molecular-anatomical characteristics.

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