Biology subjects

Jordan, C. S.

Publications and source records attributed to Jordan, C. S..

9 recordsLinked to original sources

bioRxiv2025

Connectomic reconstruction from hippocampal CA3 reveals spatially graded mossy fiber inputs and selective feedforward inhibition to pyramidal cells

The mossy fiber (MF) connections to pyramidal cells in hippocampal CA3 are hypothesized to participate in pattern separation and memory encoding, yet no large-scale neuronal wiring diagram exists for these connections. We assembled a 3D electron microscopy volume ([~]1x1x0.1mm3) from mouse hippocampal CA3. By proofreading and automated segmentation, we reconstructed and classified all soma-containing neurons--including 1,815 pyramidal cells and 229 inhibitory cells--and over 55,000 MFs. Pyramidal cells receive more numerous MF inputs along a proximodistal gradient. Some distal cells show surprisingly high convergence via relatively small terminals with fewer vesicles. Pyramidal cells share significantly more MF inputs than networks randomized by degree-preserving swap, and are better approximated by networks randomized by proximity-preserving swap. We identify a feedforward inhibitory circuit from MFs via perisomatic interneurons that selectively target a pyramidal subtype. We demonstrated large-scale mapping across levels in the hippocampus--from circuits to cell types to vesicles. The dataset is shared through Pyr, an online platform for hippocampal connectomics.

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bioRxiv2023

Neuronal wiring diagram of an adult brain

Connections between neurons can be mapped by acquiring and analyzing electron microscopic (EM) brain images. In recent years, this approach has been applied to chunks of brains to reconstruct local connectivity maps that are highly informative, yet inadequate for understanding brain function more globally. Here, we present the first neuronal wiring diagram of a whole adult brain, containing 5x107 chemical synapses between [~]130,000 neurons reconstructed from a female Drosophila melanogaster. The resource also incorporates annotations of cell classes and types, nerves, hemilineages, and predictions of neurotransmitter identities. Data products are available by download, programmatic access, and interactive browsing and made interoperable with other fly data resources. We show how to derive a projectome, a map of projections between regions, from the connectome. We demonstrate the tracing of synaptic pathways and the analysis of information flow from inputs (sensory and ascending neurons) to outputs (motor, endocrine, and descending neurons), across both hemispheres, and between the central brain and the optic lobes. Tracing from a subset of photoreceptors all the way to descending motor pathways illustrates how structure can uncover putative circuit mechanisms underlying sensorimotor behaviors. The technologies and open ecosystem of the FlyWire Consortium set the stage for future large-scale connectome projects in other species.

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bioRxiv2023

Synaptic architecture of leg and wing motor control networks in Drosophila

Animal movement is controlled by motor neurons (MNs), which project out of the central nervous system to activate muscles. MN activity is coordinated by complex premotor networks that allow individual muscles to contribute to many different behaviors. Here, we use connectomics to analyze the wiring logic of premotor circuits controlling the Drosophila leg and wing. We find that both premotor networks cluster into modules that link MNs innervating muscles with related functions. Within most leg motor modules, the synaptic weights of each premotor neuron are proportional to the size of their target MNs, establishing a circuit basis for hierarchical MN recruitment. In contrast, wing premotor networks lack proportional synaptic connectivity, which may allow wing steering muscles to be recruited with different relative timing. By comparing the architecture of distinct limb motor control systems within the same animal, we identify common principles of premotor network organization and specializations that reflect the unique biomechanical constraints and evolutionary origins of leg and wing motor control.

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bioRxiv2022

Tools for comprehensive reconstruction and analysis of Drosophila motor circuits

Like the vertebrate spinal cord, the insect ventral nerve cord (VNC) mediates limb sensation and motor control. Here, we apply automated tools for electron microscopy volume alignment, neuron segmentation, and synapse prediction toward creating a connectome of an adult female Drosophila VNC. To interpret a connectome, it is crucial to know its relationship with the rest of the body. We therefore mapped the muscle targets of leg and wing motor neurons in the connectome by comparing their morphology to genetic driver lines, dye fills, and X-ray nano-tomography of the fly leg and wing. Knowing the outputs of the connectome allowed us to identify neural circuits that coordinate the wings and legs during escape takeoff. We provide the reconstruction of VNC circuits and motor neuron atlas, along with tools for programmatic and interactive access, as community resources to support experimental and theoretical studies of how the fly nervous system controls behavior.

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bioRxiv2022

Special Nuclear Layer Contacts Among Starburst Amacrine Cells in the Mouse Retina

We observed novel classes of cell-cell contacts between retinal starburst amacrine neurons, from finely detailed morphological reconstructions of cells from an electron microscopic image volume of a mouse retina. These contacts have peculiar morphological patterns and traits, different among the respective On and Off starburst amacrine subpopulations, but both occur within the soma layers as opposed to their regular laminae of contact within the inner plexiform layer.

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bioRxiv2021

Oligodendrocyte precursor cells prune axons in the mouse neocortex

Neurons in the developing brain undergo extensive structural refinement as nascent circuits adopt their mature form1. This transformation is facilitated by the engulfment and degradation of excess axonal branches and inappropriate synapses by surrounding glial cells, including microglia and astrocytes2,3. However, the small size of phagocytic organelles and the complex, highly ramified morphology of glia has made it difficult to determine the contribution of these and other glial cell types to this process. Here, we used large scale, serial electron microscopy (ssEM) with computational volume segmentation to reconstruct the complete 3D morphologies of distinct glial types in the mouse visual cortex. Unexpectedly, we discovered that the fine processes of oligodendrocyte precursor cells (OPCs), a population of abundant, highly dynamic glial progenitors4, frequently surrounded terminal axon branches and included numerous phagolysosomes (PLs) containing fragments of axons and presynaptic terminals. Single- nucleus RNA sequencing indicated that cortical OPCs express key phagocytic genes, as well as neuronal transcripts, consistent with active axonal engulfment. PLs were ten times more abundant in OPCs than in microglia in P36 mice, and declined with age and lineage progression, suggesting that OPCs contribute very substantially to refinement of neuronal circuits during later phases of cortical development.

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bioRxiv2020

Modularity and neural coding from a brainstem synaptic wiring diagram

How much can connectomes with synaptic resolution help us understand brain function? An optimistic view is that a connectome is a major determinant of brain function and a key substrate for simulating a brain. Here we investigate the explanatory power of connectomics using a wiring diagram reconstructed from a larval zebrafish brainstem. We identify modules of strongly connected neurons that turn out to be specialized for different behavioral functions, the control of eye and body movements. We then build a neural network model using a synaptic weight matrix based on the reconstructed wiring diagram. This leads to predictions that statistically match the neural coding of eye position as observed by calcium imaging. Our work shows the promise of connectome-based brain modeling to yield experimentally testable predictions of neural activity and behavior, as well as mechanistic explanations of low-dimensional neural dynamics, a widely observed phenomenon in nervous systems.

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bioRxiv2020

Multiscale and multimodal reconstruction of cortical structure and function

We present a semi-automated reconstruction of L2/3 mouse primary visual cortex from 3 million cubic microns of electron microscopic images, including pyramidal and inhibitory neurons, astrocytes, microglia, oligodendrocytes and precursors, pericytes, vasculature, mitochondria, and synapses. Visual responses of a subset of pyramidal cells are included. The data are being made publicly available, along with tools for programmatic and 3D interactive access. The density of synaptic inputs onto inhibitory neurons varies across cell classes and compartments. We uncover a compartment-specific correlation between mitochondrial coverage and synapse density. Frequencies of connectivity motifs in the graph of pyramidal cells are predicted quite accurately from node degrees using the configuration model of random graphs. Cells receiving more connections from nearby cells exhibit stronger and more reliable visual responses. These example findings illustrate the resources utility for relating structure and function of cortical circuits as well as for neuronal cell biology.

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bioRxiv2017

Structural and functional diversity of a dense sample of retinal ganglion cells

To aid understanding of retinal structure and function, we present as an online resource the dendritic arbors and visual responses of ganglion cells in a single patch of mouse retina. We divide the inner plexiform layer, which contains the dendritic arbors of ganglion cells, into four sublaminae defined by a purely anatomical principle of arbor segregation. The sublaminae serve as the starting point for a hierarchical clustering of our ganglion cells. We propose and apply a quantitative criterion for validating a cluster as a ganglion cell type: the aggregate neurite density of a type should be approximately uniform (\"density conservation\"). Finally, we find that ganglion cells arborizing in the inner marginal sublamina of the inner plexi-form layer exhibit significantly more sustained visual responses on average.

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