Biology subjects

Collman, F. C.

Publications and source records attributed to Collman, F. C..

6 recordsLinked to original sources

bioRxiv2026

Cell-type-specific parallel pathways in the canonical cortical microcircuit

Information processing in the cortex depends on the integration of bottom-up and top-down signals through recurrent microcircuits spanning layers. Although the canonical microcircuit provides a framework for this integration, how these interactions are implemented at synapse resolution remains unclear. Here, we use large-volume electron microscopy reconstructions of mouse primary visual cortex to map the intralaminar and interlaminar connectivity of intratelencephalic (IT) neurons in layers 2/3 and 5. We find that layer 2/3 IT neurons formed a depth-dependent gradient of recurrent connectivity, with superficial (L2) and deeper (L3) neurons potentially forming two channels associated with top-down and bottom-up processing, respectively. These channels are preserved across layers via cell-type-specific pathways involving distinct L5 IT types, rather than collapsing into a single integrative pool. Moreover, each channel is regulated by a largely separate cohort of inhibitory interneurons, stabilizing recurrent excitation while limiting crosstalk. Together, these results reveal parallel, cell-type-specific processing streams embedded within the canonical circuit.

neuroscience↗

bioRxiv2026

A central somatotopic map of the fly leg supports spatially targeted grooming

Animals continuously monitor their body surfaces to detect and remove debris or parasites. Effective grooming requires that tactile inputs from specific body regions be converted into precisely targeted motor actions, but the neural circuits that support this sensorimotor transformation remain poorly understood. Here, we combine genetic tools and connectomics to elucidate a central somatotopic map of the Drosophila leg. We show that the axonal projections of leg touch receptors within the flys ventral nerve cord (VNC) are organized along the same cardinal axes as the developing leg. Somatotopically organized bristle axons target a specific class of developmentally-related local interneurons, which imbricate the leg map with overlapping receptive fields of different shapes and sizes. These second-order interneurons target distinct pools of premotor interneurons, which in turn synapse directly onto motor neurons that control leg muscles. Optogenetic activation of second-order interneurons elicits spatially targeted grooming of specific leg regions, consistent with our spatial receptive field predictions based on the connectome. Together, our results suggest that this four-layer circuit processes spatial information from a somatotopic map of the fly leg to guide targeted grooming behavior.

neuroscience↗

bioRxiv2023

Nanometer-scale views of visual cortex reveal anatomical features of primary cilia poised to detect synaptic spillover

A primary cilium is a thin membrane-bound extension off a cell surface that contains receptors for perceiving and transmitting signals that modulate cell state and activity. While many cell types have a primary cilium, little is known about primary cilia in the brain, where they are less accessible than cilia on cultured cells or epithelial tissues and protrude from cell bodies into a deep, dense network of glial and neuronal processes. Here, we investigated cilia frequency, internal structure, shape, and position in large, high-resolution transmission electron microscopy volumes of mouse primary visual cortex. Cilia extended from the cell bodies of nearly all excitatory and inhibitory neurons, astrocytes, and oligodendrocyte precursor cells (OPCs), but were absent from oligodendrocytes and microglia. Structural comparisons revealed that the membrane structure at the base of the cilium and the microtubule organization differed between neurons and glia. OPC cilia were distinct in that they were the shortest and contained pervasive internal vesicles only occasionally observed in neuron and astrocyte cilia. Investigating cilia-proximal features revealed that many cilia were directly adjacent to synapses, suggesting cilia are well poised to encounter locally released signaling molecules. Cilia proximity to synapses was random, not enriched, in the synapse-rich neuropil. The internal anatomy, including microtubule changes and centriole location, defined key structural features including cilium placement and shape. Together, the anatomical insights both within and around neuron and glia cilia provide new insights into cilia formation and function across cell types in the brain.

cell biology↗

bioRxiv2023

Developing a Toolbox of Antibodies Validated for Array Tomography-Based Imaging of Brain Synapses

Antibody-based imaging techniques rely on reagents whose performance may be application-specific. Because commercial antibodies are validated for only a few purposes, users interested in other applications may have to perform extensive in-house antibody testing. Here we present a novel application-specific proxy screening step to efficiently identify candidate antibodies for array tomography (AT), a serial section volume microscopy technique for high-dimensional quantitative analysis of the cellular proteome. To identify antibodies suitable for AT-based analysis of synapses in mammalian brain, we introduce a heterologous cell-based assay that simulates characteristic features of AT, such as chemical fixation and resin embedding that are likely to influence antibody binding. The assay was included into an initial screening strategy to generate monoclonal antibodies that can be used for AT. This approach simplifies the screening of candidate antibodies and has high predictive value for identifying antibodies suitable for AT analyses. In addition, we have created a comprehensive database of AT-validated antibodies with a neuroscience focus and show that these antibodies have a high likelihood of success for postembedding applications in general, including immunogold electron microscopy. The generation of a large and growing toolbox of AT-compatible antibodies will further enhance the value of this imaging technique. Significance StatementArray tomography (AT) is a powerful volume microscopy technique for high-dimensional analysis of complex protein populations in cells and organelles, including synapses. AT involves the use of ultrathin serial sections embedded in resin and subjected to multiple rounds of immunofluorescence antibody (Ab) labeling and imaging. AT relies on antibody-based detection of proteins but because commercial antibodies are typically validated for other applications they often fail for AT. To identify antibodies with high probability of success in AT we developed a novel screening strategy and used this to create a comprehensive database of AT-validated antibodies for neuroscience.

neuroscience↗

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.

neuroscience↗

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.

neuroscience↗