scholarly journals Genetic Single Neuron Anatomy reveals fine granularity of cortical interneuron subtypes

2017 ◽  
Author(s):  
Xiaojun Wang ◽  
Jason Tucciarone ◽  
Siqi Jiang ◽  
Fangfang Yin ◽  
Bor-shuen Wang ◽  
...  
Keyword(s):  
Single Neuron ◽  
Neural Circuit ◽  
Morphological Diversity ◽  
Gabaergic Interneuron ◽  
Local Geometry ◽  
Fine Grained ◽  
Axonal Arborization ◽  
Cell Groups ◽  
Intuitive Criterion ◽  
Genetic Labeling

AbstractParsing diverse nerve cells into biological types is necessary for understanding neural circuit organization. Morphology is an intuitive criterion for neuronal classification and a proxy of connectivity, but morphological diversity and variability often preclude resolving the granularity of discrete cell groups from population continuum. Combining genetic labeling with high-resolution, large volume light microscopy, we established a platform of genetic single neuron anatomy that resolves, registers and quantifies complete neuron morphologies in the mouse brain. We discovered that cortical axo-axonic cells (AACs), a cardinal GABAergic interneuron type that controls pyramidal neuron (PyN) spiking at axon initial segment, consist of multiple subtypes distinguished by laminar position, dendritic and axonal arborization patterns. Whereas the laminar arrangements of AAC dendrites reflect differential recruitment by input streams, the laminar distribution and local geometry of AAC axons enable differential innervation of PyN ensembles. Therefore, interneuron types likely consist of fine-grained subtypes with distinct input-output connectivity patterns.

scholarly journals Implications of Extended Inhibitory Neuron Development

2021 ◽  
Vol 22 (10) ◽  
pp. 5113
Author(s):  
Jae-Yeon Kim ◽  
Mercedes F. Paredes
Keyword(s):  
Neural Circuit ◽  
Inhibitory Neuron ◽  
Postnatal Period ◽  
Specific Pattern ◽  
Inhibitory Neurons ◽  
Gabaergic Interneuron ◽  
Gabaergic Interneurons ◽  
Neuron Development ◽  
Cortical Regions ◽  
Circuit Formation

A prolonged developmental timeline for GABA (γ-aminobutyric acid)-expressing inhibitory neurons (GABAergic interneurons) is an amplified trait in larger, gyrencephalic animals. In several species, the generation, migration, and maturation of interneurons take place over several months, in some cases persisting after birth. The late integration of GABAergic interneurons occurs in a region-specific pattern, especially during the early postnatal period. These changes can contribute to the formation of functional connectivity and plasticity, especially in the cortical regions responsible for higher cognitive tasks. In this review, we discuss GABAergic interneuron development in the late gestational and postnatal forebrain. We propose the protracted development of interneurons at each stage (neurogenesis, neuronal migration, and network integration), as a mechanism for increased complexity and cognitive flexibility in larger, gyrencephalic brains. This developmental feature of interneurons also provides an avenue for environmental influences to shape neural circuit formation.

Precerebellar Cell Groups in the Hindbrain of the Mouse Defined by Retrograde Tracing and Correlated with Cumulative Wnt1-Cre Genetic Labeling

2011 ◽  
Vol 10 (3) ◽  
pp. 570-584 ◽  
Author(s):  
YuHong Fu ◽  
Petr Tvrdik ◽  
Nadja Makki ◽  
George Paxinos ◽  
Charles Watson
Keyword(s):  
Retrograde Tracing ◽  
Cell Groups ◽  
Genetic Labeling

scholarly journals High-throughput mapping of single-cell molecular and projection architecture of neurons by retrograde barcoded labelling

2021 ◽  
Author(s):  
Peibo Xu ◽  
Jian Peng ◽  
Tingli Yuan ◽  
Zhaoqin Chen ◽  
Ziyan Wu ◽  
...  
Keyword(s):  
Single Cell ◽  
Single Neuron ◽  
Neural Circuit ◽  
Brain Regions ◽  
Mammalian Brain ◽  
Projection Neurons ◽  
Proof Of Concept ◽  
Sequencing Technology ◽  
Modal Data ◽  
Projection Pattern

Deciphering mesoscopic connectivity of the mammalian brain is a pivotal step in neuroscience. Most imaging-based conventional neuroanatomical tracing methods identify area-to-area or sparse single neuronal labeling information. Although recently developed barcode-based connectomics has been able to map a large number of single-neuron projections efficiently, there is a missing link in single-cell connectome and transcriptome. Here, combining single-cell RNA sequencing technology, we established a retro-AAV barcode-based multiplexed tracing method called MEGRE-seq (Multiplexed projEction neuRons retroGrade barcodE), which can resolve projectome and transcriptome of source neurons simultaneously. Using the ventromedial prefrontal cortex (vmPFC) as a proof-of-concept neocortical region, we investigated projection patterns of its excitatory neurons targeting five canonical brain regions, as well as corresponding transcriptional profiles. Dedicated, bifurcated or collateral projection patterns were inferred by digital projectome. In combination with simultaneously recovered transcriptome, we find that certain projection pattern has a preferential layer or neuron subtype bias. Further, we fitted single-neuron two-modal data into a machine learning-based model and delineated gene importance by each projection target. In summary, we anticipate that the new multiplexed digital connectome technique is potential to understand the organizing principle of the neural circuit by linking projectome and transcriptome.

scholarly journals Neuropeptide VF neurons promote sleep via the serotonergic raphe

2019 ◽  
Author(s):  
Daniel A. Lee ◽  
Grigorios Oikonomou ◽  
Tasha Cammidge ◽  
Young Hong ◽  
David A. Prober
Keyword(s):  
Calcium Imaging ◽  
Neural Circuit ◽  
Raphe Nuclei ◽  
Hypothalamic Neurons ◽  
Optogenetic Stimulation ◽  
Genetic Epistasis ◽  
Normal Sleep ◽  
Genetic Labeling ◽  
Raphé Nuclei ◽  
Stimulation Of

ABSTRACTAlthough several sleep-regulating neurons have been identified, little is known about how they interact with each other for sleep/wake control. We previously identified neuropeptide VF (NPVF) and the hypothalamic neurons that produce it as a sleep-promoting system (Lee et al., 2017). Here we use zebrafish to describe a neural circuit in which neuropeptide VF (npvf)-expressing neurons control sleep via the serotonergic raphe nuclei (RN), a hindbrain structure that promotes sleep in both diurnal zebrafish and nocturnal mice. Using genetic labeling and calcium imaging, we show that npvf-expressing neurons innervate and activate serotonergic RN neurons. We additionally demonstrate that optogenetic stimulation of npvf-expressing neurons induces sleep in a manner that requires NPVF and is abolished when the RN are ablated or lack serotonin. Finally, genetic epistasis demonstrates that NPVF acts upstream of serotonin in the RN to maintain normal sleep levels. These findings reveal a novel hypothalamic-hindbrain circuit for sleep/wake control.

scholarly journals Brain-wide single neuron reconstruction reveals morphological diversity in molecularly defined striatal, thalamic, cortical and claustral neuron types

2020 ◽  
Author(s):  
Hanchuan Peng ◽  
Peng Xie ◽  
Lijuan Liu ◽  
Xiuli Kuang ◽  
Yimin Wang ◽  
...  
Keyword(s):  
Single Neuron ◽  
Morphological Diversity ◽  
Cell Types ◽  
Fluorescent Labeling ◽  
Computer Assisted ◽  
Large Set ◽  
Whole Brain ◽  
Wide Range ◽  
Neuronal Types ◽  
Organizational Rules

Abstract Ever since the seminal findings of Ramon y Cajal, dendritic and axonal morphology has been recognized as a defining feature of neuronal types. Yet our knowledge concerning the diversity of neuronal morphologies, in particular distal axonal projection patterns, is extremely limited. To systematically obtain single neuron full morphology on a brain-wide scale, we established a platform with five major components: sparse labeling, whole-brain imaging, reconstruction, registration, and classification. We achieved sparse, robust and consistent fluorescent labeling of a wide range of neuronal types by combining transgenic or viral Cre delivery with novel transgenic reporter lines. We acquired high-resolution whole-brain fluorescent images from a large set of sparsely labeled brains using fluorescence micro-optical sectioning tomography (fMOST). We developed a set of software tools for efficient large-volume image data processing, registration to the Allen Mouse Brain Common Coordinate Framework (CCF), and computer-assisted morphological reconstruction. We reconstructed and analyzed the complete morphologies of 1,708 neurons from the striatum, thalamus, cortex and claustrum. Finally, we classified these cells into multiple morphological and projection types and identified a set of region-specific organizational rules of long-range axonal projections at the single cell level. Specifically, different neuron types from different regions follow highly distinct rules in convergent or divergent projection, feedforward or feedback axon termination patterns, and between-cell homogeneity or heterogeneity. Major molecularly defined classes or types of neurons have correspondingly distinct morphological and projection patterns, however, we also identify further remarkably extensive morphological and projection diversity at more fine-grained levels within the major types that cannot presently be accounted for by preexisting transcriptomic subtypes. These insights reinforce the importance of full morphological characterization of brain cell types and suggest a plethora of ways different cell types and individual neurons may contribute to the function of their respective circuits.

scholarly journals Brain-wide single neuron reconstruction reveals morphological diversity in molecularly defined striatal, thalamic, cortical and claustral neuron types

2019 ◽  
Author(s):  
Hanchuan Peng ◽  
Peng Xie ◽  
Lijuan Liu ◽  
Xiuli Kuang ◽  
Yimin Wang ◽  
...  
Keyword(s):  
Single Neuron ◽  
Morphological Diversity ◽  
Cell Types ◽  
Fluorescent Labeling ◽  
Computer Assisted ◽  
Large Set ◽  
Whole Brain ◽  
Wide Range ◽  
Neuronal Types ◽  
Organizational Rules

ABSTRACTEver since the seminal findings of Ramon y Cajal, dendritic and axonal morphology has been recognized as a defining feature of neuronal types. Yet our knowledge concerning the diversity of neuronal morphologies, in particular distal axonal projection patterns, is extremely limited. To systematically obtain single neuron full morphology on a brain-wide scale, we established a platform with five major components: sparse labeling, whole-brain imaging, reconstruction, registration, and classification. We achieved sparse, robust and consistent fluorescent labeling of a wide range of neuronal types by combining transgenic or viral Cre delivery with novel transgenic reporter lines. We acquired high-resolution whole-brain fluorescent images from a large set of sparsely labeled brains using fluorescence micro-optical sectioning tomography (fMOST). We developed a set of software tools for efficient large-volume image data processing, registration to the Allen Mouse Brain Common Coordinate Framework (CCF), and computer-assisted morphological reconstruction. We reconstructed and analyzed the complete morphologies of 1,708 neurons from the striatum, thalamus, cortex and claustrum. Finally, we classified these cells into multiple morphological and projection types and identified a set of region-specific organizational rules of long-range axonal projections at the single cell level. Specifically, different neuron types from different regions follow highly distinct rules in convergent or divergent projection, feedforward or feedback axon termination patterns, and between-cell homogeneity or heterogeneity. Major molecularly defined classes or types of neurons have correspondingly distinct morphological and projection patterns, however, we also identify further remarkably extensive morphological and projection diversity at more fine-grained levels within the major types that cannot presently be accounted for by preexisting transcriptomic subtypes. These insights reinforce the importance of full morphological characterization of brain cell types and suggest a plethora of ways different cell types and individual neurons may contribute to the function of their respective circuits.

scholarly journals NBLAST: Rapid, sensitive comparison of neuronal structure and construction of neuron family databases

2014 ◽  
Author(s):  
Marta Costa ◽  
James D. Manton ◽  
Aaron D. Ostrovsky ◽  
Steffen Prohaska ◽  
Gregory S. X. E. Jefferis
Keyword(s):  
Transgene Expression ◽  
Neural Circuit ◽  
A Priori ◽  
Expression Patterns ◽  
Validation Dataset ◽  
Local Geometry ◽  
Neuronal Structure ◽  
Computational Tools ◽  
Neuronal Types ◽  
Scoring Matrix

AbstractNeural circuit mapping is generating datasets of 10,000s of labeled neurons. New computational tools are needed to search and organize these data. We present NBLAST, a sensitive and rapid algorithm, for measuring pairwise neuronal similarity. NBLAST considers both position and local geometry, decomposing neurons into short segments; matched segments are scored using a probabilistic scoring matrix defined by statistics of matches and non-matches.We validated NBLAST on a published dataset of 16,129 single Drosophila neurons. NBLAST can distinguish neuronal types down to the finest level (single identified neurons) without a priori information. Cluster analysis of extensively studied neuronal classes identified new types and un-reported topographical features. Fully automated clustering organized the validation dataset into 1052 clusters, many of which map onto previously described neuronal types. NBLAST supports additional query types including searching neurons against transgene expression patterns. Finally we show that NBLAST is effective with data from other invertebrates and zebrafish.

scholarly journals GABAergic motor neurons bias locomotor decision-making in C. elegans

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ping Liu ◽  
Bojun Chen ◽  
Zhao-Wen Wang
Keyword(s):  
Decision Making ◽  
Motor Neurons ◽  
Gaba Receptor ◽  
Single Neuron ◽  
Neural Circuit ◽  
Electrical Coupling ◽  
C Elegans ◽  
Sensory Modalities ◽  
Motor Information ◽  
Molecular Bases

Abstract Proper threat-reward decision-making is critical to animal survival. Emerging evidence indicates that the motor system may participate in decision-making but the neural circuit and molecular bases for these functions are little known. We found in C. elegans that GABAergic motor neurons (D-MNs) bias toward the reward behavior in threat-reward decision-making by retrogradely inhibiting a pair of premotor command interneurons, AVA, that control cholinergic motor neurons in the avoidance neural circuit. This function of D-MNs is mediated by a specific ionotropic GABA receptor (UNC-49) in AVA, and depends on electrical coupling between the two AVA interneurons. Our results suggest that AVA are hub neurons where sensory inputs from threat and reward sensory modalities and motor information from D-MNs are integrated. This study demonstrates at single-neuron resolution how motor neurons may help shape threat-reward choice behaviors through interacting with other neurons.

scholarly journals Drosulfakinin signaling in fruitless circuitry antagonizes P1 neurons to regulate sexual arousal in Drosophila

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Shunfan Wu ◽  
Chao Guo ◽  
Huan Zhao ◽  
Mengshi Sun ◽  
Jie Chen ◽  
...  
Keyword(s):  
Sexual Behaviors ◽  
Single Neuron ◽  
Neural Circuits ◽  
Neural Circuit ◽  
Neural Substrates ◽  
Internal States ◽  
And Function ◽  
Key Steps ◽  
Male Specific ◽  
Command Center

Abstract Animals perform or terminate particular behaviors by integrating external cues and internal states through neural circuits. Identifying neural substrates and their molecular modulators promoting or inhibiting animal behaviors are key steps to understand how neural circuits control behaviors. Here, we identify the Cholecystokinin-like peptide Drosulfakinin (DSK) that functions at single-neuron resolution to suppress male sexual behavior in Drosophila. We found that Dsk neurons physiologically interact with male-specific P1 neurons, part of a command center for male sexual behaviors, and function oppositely to regulate multiple arousal-related behaviors including sex, sleep and spontaneous walking. We further found that the DSK-2 peptide functions through its receptor CCKLR-17D3 to suppress sexual behaviors in flies. Such a neuropeptide circuit largely overlaps with the fruitless-expressing neural circuit that governs most aspects of male sexual behaviors. Thus DSK/CCKLR signaling in the sex circuitry functions antagonistically with P1 neurons to balance arousal levels and modulate sexual behaviors.

scholarly journals Residual dynamics resolves recurrent contributions to neural computation

2021 ◽  
Author(s):  
Aniruddh R Galgali ◽  
Maneesh Sahani ◽  
Valerio Mante
Keyword(s):  
Decision Making ◽  
Large Scale ◽  
Neural Circuit ◽  
Neural Population ◽  
Perceptual Decision Making ◽  
Neural Recordings ◽  
Fine Grained ◽  
Neural Computations ◽  
Population Trajectory ◽  
The Mean

Relating neural activity to behavior requires an understanding of how neural computations arise from the coordinated dynamics of distributed, recurrently connected neural populations. However, inferring the nature of recurrent dynamics from partial recordings of a neural circuit presents significant challenges. Here, we show that some of these challenges can be overcome by a fine-grained analysis of the dynamics of neural residuals, i.e. trial-by-trial variability around the mean neural population trajectory for a given task condition. Residual dynamics in macaque pre-frontal cortex (PFC) in a saccade-based perceptual decision-making task reveals recurrent dynamics that is time-dependent, but consistently stable, and implies that pronounced rotational structure in PFC trajectories during saccades are driven by inputs from upstream areas. The properties of residual dynamics restrict the possible contributions of PFC to decision-making and saccade generation, and suggest a path towards fully characterizing distributed neural computations with large-scale neural recordings and targeted causal perturbations.

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