Biology subjects

Schneider-Mizell, C. M.

Publications and source records attributed to Schneider-Mizell, C. M..

25 records · Page 2Linked to original sources

bioRxiv2021

Functional connectomics spanning multiple areas of mouse visual cortex

To understand the brain we must relate neurons functional responses to the circuit architecture that shapes them. Here, we present a large functional connectomics dataset with dense calcium imaging of a millimeter scale volume. We recorded activity from approximately 75,000 neurons in primary visual cortex (VISp) and three higher visual areas (VISrl, VISal and VISlm) in an awake mouse viewing natural movies and synthetic stimuli. The functional data were co-registered with a volumetric electron microscopy (EM) reconstruction containing more than 200,000 cells and 0.5 billion synapses. Subsequent proofreading of a subset of neurons in this volume yielded reconstructions that include complete dendritic trees as well the local and inter-areal axonal projections that map up to thousands of cell-to-cell connections per neuron. Here, we release this dataset as an open-access resource to the scientific community including a set of tools that facilitate data retrieval and downstream analysis. In accompanying papers we describe our findings using the dataset to provide a comprehensive structural characterization of cortical cell types1-3 and the most detailed synaptic level connectivity diagram of a cortical column to date2, uncovering unique cell-type specific inhibitory motifs that can be linked to gene expression data4. Functionally, we identify new computational principles of how information is integrated across visual space5, characterize novel types of neuronal invariances6 and bring structure and function together to decipher a general principle that wires excitatory neurons within and across areas7, 8.

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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

Unveiling the sensory and interneuronal pathways of the neuroendocrine system in Drosophila

Neuroendocrine systems in animals maintain organismal homeostasis and regulate stress response. Although a great deal of work has been done on the neuropeptides and hormones that are released and act on target organs in the periphery, the synaptic inputs onto these neuroendocrine outputs in the brain are less well understood. Here, we use the transmission electron microscopy reconstruction of a whole central nervous system in the Drosophila larva to elucidate the sensory pathways and the interneurons that provide synaptic input to the neurosecretory cells projecting to the endocrine organs. Predicted by network modeling, we also identify a new carbon dioxide responsive network that acts on a specific set of neurosecretory cells and which include those expressing Corazonin (Crz) and Diuretic hormone 44 (DH44) neuropeptides. Our analysis reveals a neuronal network architecture for combinatorial action based on sensory and interneuronal pathways that converge onto distinct combinations of neuroendocrine outputs.

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bioRxiv2020

Chandelier cell anatomy and function reveal a variably distributed but common signal

The activity and connectivity of inhibitory cells has a profound impact on the operation of neuronal networks. While the average connectivity of many inhibitory cell types has been characterized, we still lack an understanding of how individual interneurons distribute their synapses onto their targets and how heterogeneous the inhibition is onto different individual excitatory neurons. Here, we use large-scale volumetric electron microscopy (EM) and functional imaging to address this question for chandelier cells in layer 2/3 of mouse visual cortex. Using dense morphological reconstructions from EM, we mapped the complete chandelier input onto 153 pyramidal neurons. We find that the number of input synapses is highly variable across the population, but the variability is correlated with structural features of the target neuron: soma depth, soma size, and the number of perisomatic synapses received. Functionally, we found that chandelier cell activity in vivo was highly correlated and tracks pupil diameter, a proxy for arousal state. We propose that chandelier cells provide a global signal whose strength is individually adjusted for each target neuron. This approach, combining comprehensive structural analysis with functional recordings of identified cell types, will be a powerful tool to uncover the wiring rules across the diversity of cortical cell types.

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bioRxiv2018

The Feeding Connectome: Convergence of Monosynaptic and Polysynaptic Sensory Paths onto Common Motor Outputs

Little is known about the organization of central circuits by which external and internal sensory inputs act on motor outputs to regulate fundamental behaviors such as feeding. We reconstructed, from a whole CNS EM volume, the synaptic map of input and output neurons that underlie food intake behavior of Drosophila larvae. The input neurons originate from enteric, pharyngeal and external sensory organs and converge onto seven distinct sensory synaptic compartments within the CNS, as defined by distribution patterns of their presynaptic sites. The output neurons consist of pharyngeal motor neurons, serotonergic modulatory neurons, and neuroendocrine neurons that target the ring gland, a key endocrine organ. Monosynaptic connections from a set of sensory synaptic compartments cover the motor and endocrine targets in overlapping domains. Polysynaptic routes can be superimposed on top of the monosynaptic connections, resulting in divergent sensory paths that converge on common motor outputs. A completely different set of sensory compartments is connected to the mushroom body calyx of the memory circuits. Our results illustrate a circuit architecture in which monosynaptic and multisynaptic connections from sensory inputs traverse onto output neurons via a series of converging paths.

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bioRxiv2017

Conserved Neural Circuit Structure Across Drosophila Larva Development Revealed By Comparative Connectomics

Throughout an animals postembryonic development, neuronal circuits must maintain appropriate output even as the body grows. The contribution of structural adaptation -- neuronal morphology and synaptic connectivity -- to circuit development remains unclear. In a previous paper (Schneider-Mizell et al., 2016), we measured the detailed neuronal morphological structures subserving neuronal connectivity in Drosophila. Here, we examine how neuronal morphology and connectivity change across postembyronic development. Using new and existing serial section electron microscopy volumes, we reconstructed an identified nociceptive circuit in two larvae, one 1st instar and one 3rd instar. We found extremely consistent, topographically-arranged circuit structure. Five-fold increases in size of interneurons were associated with compensatory structural changes that maintained cell-type-specific synaptic input as a fraction of total inputs. An increase in number of synaptic contacts was accompanied with a disproportionate increase in the number of small dendritic terminal branches relative to other neuronal compartments. We propose that these precise patterns of structural growth act to conserve the computational function of a circuit, for example determining the location of a nociceptive stimulus.

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bioRxiv2017

The Complete Connectome Of A Learning And Memory Center In An Insect Brain

Associating stimuli with positive or negative reinforcement is essential for survival, but a complete wiring diagram of a higherorder circuit supporting associative memory has not been previously available. We reconstructed one such circuit at synaptic resolution, the Drosophila larval mushroom body, and found that most Kenyon cells integrate random combinations of inputs but a subset receives stereotyped inputs from single projection neurons. This organization maximizes performance of a model output neuron on a stimulus discrimination task. We also report a novel canonical circuit in each mushroom body compartment with previously unidentified connections: reciprocal Kenyon cell to modulatory neuron connections, modulatory neuron to output neuron connections, and a surprisingly high number of recurrent connections between Kenyon cells. Stereotyped connections between output neurons could enhance the selection of learned responses. The complete circuit map of the mushroom body should guide future functional studies of this learning and memory center.

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