Biology subjects

Heckman, E. L.

Publications and source records attributed to Heckman, E. L..

5 recordsLinked to original sources

bioRxiv2023

Diversity of visual inputs to Kenyon cells of the Drosophila mushroom body

The arthropod mushroom body is well-studied as an expansion layer that represents olfactory stimuli and links them to contingent events. However, 8% of mushroom body Kenyon cells in Drosophila melanogaster receive predominantly visual input, and their tuning and function are poorly understood. Here, we use the FlyWire adult whole-brain connectome to identify inputs to visual Kenyon cells. The types of visual neurons we identify are similar across hemispheres and connectomes with certain inputs highly overrepresented. Many visual projection neurons presynaptic to Kenyon cells receive input from large swathes of visual space, while local visual interneurons, providing smaller fractions of input, receive more spatially restricted signals that may be tuned to specific features of the visual scene. Like olfactory Kenyon cells, visual Kenyon cells receive sparse inputs from different combinations of visual channels, including inputs from multiple optic lobe neuropils. The sets of inputs to individual visual Kenyon cells are consistent with random sampling of available inputs. These connectivity patterns suggest that visual coding in the mushroom body, like olfactory coding, is sparse, distributed, and combinatorial. However, the expansion coding properties appear different, with a specific repertoire of visual inputs projecting onto a relatively small number of visual Kenyon cells.

neuroscience↗

bioRxiv2022

Presynaptic contact and activity opposingly regulate postsynaptic dendrite outgrowth

The organization of neural circuits determines nervous system function. Variability can arise during neural circuit development (e.g. neurite morphology, axon/dendrite position). To ensure robust nervous system function, mechanisms must exist to accommodate variation in neurite positioning during circuit formation. Previously we developed a model system in the Drosophila ventral nerve cord to conditionally induce positional variability of a proprioceptive sensory axon terminal, and used this model to show that when we altered the presynaptic position of the sensory neuron, its major postsynaptic interneuron partner modified its dendritic arbor to match the presynaptic contact, resulting in functional synaptic input (Sales et al., 2019). Here we investigate the cellular mechanisms by which the interneuron dendrites detect and match variation in presynaptic partner location and input strength. We manipulate the presynaptic sensory neuron by (a) ablation; (b) silencing or activation; or (c) altering its location in the neuropil. From these experiments we conclude that there are two opposing mechanisms used to establish functional connectivity in the face of presynaptic variability: presynaptic contact stimulates dendrite outgrowth locally, whereas presynaptic activity inhibits postsynaptic dendrite outgrowth globally. These mechanisms are only active during an early larval critical period for structural plasticity. Collectively, our data provide new insights into dendrite development, identifying mechanisms that allow dendrites to flexibly and robustly respond to developmental variability in presynaptic location and input strength.

neuroscience↗

bioRxiv2021

Synapse-associated astrocyte mitochondria stabilize motor circuits to prevent excitotoxicity

Neurons have an outsized metabolic demand, requiring continuous metabolic support from non-neuronal cells called glia. When this support fails, toxic metabolic byproducts accumulate, ultimately leading to excitotoxicity and neurodegeneration. Astrocytes, the primary synapse-associated glial cell type, are known to provide essential metabolites (e.g. lactate) to sustain neuronal function. Here, we leverage the well-characterized Drosophila motor circuit to investigate another means of astrocyte-to-neuron metabolic support: activity-dependent trafficking of astrocyte mitochondria. Following optogenetic activation, motor neuron mitochondria migrate away from synapses. By contrast, astrocytic mitochondria accumulated peri-synaptically, and at times, were transferred into neighboring neurons. A genetic screen identified the mitochondrial adaptor protein Milton as a key regulator of this process. Astrocyte-specific milton knockdown disrupted regular mitochondrial trafficking, resulting in locomotor deficits, dysfunctional motor activity, and altered synapse number at the neuromuscular junction. These findings suggest that astrocytes dynamically redistribute mitochondria to buffer metabolic demand at synapses, highlighting a potential mechanism by which glia protect neural circuits from metabolic failure and neurodegeneration.

neuroscience↗

bioRxiv2019

Regulation of subcellular dendritic synapse specificity by axon guidance cues

Neural circuit assembly occurs with subcellular precision, yet the mechanisms underlying this precision remain largely unknown. Subcellular synaptic specificity could be achieved by molecularly distinct subcellular domains that locally regulate synapse formation, or by axon guidance cues restricting access to one of several acceptable targets. We address these models using two Drosophila neurons: the dbd sensory neuron and the A08a interneuron. In wild-type larvae, dbd synapses with the A08a medial dendrite but not the A08a lateral dendrite. dbd-specific overexpression of the guidance receptors Unc-5 or Robo-2 results in lateralization of the dbd axon, which forms anatomical and functional monosynaptic connections with the A08a lateral dendrite. We conclude that axon guidance cues, not molecularly distinct dendritic arbors, are a major determinant of dbd-A08a subcellular synapse specificity.

neuroscience↗

bioRxiv2017

Asymmetry of an intracellular scaffold at vertebrate electrical synapses

Neuronal synaptic connections are electrical or chemical and together are essential to dynamically defining neural circuit function. While chemical synapses are well known for their biochemical complexity, electrical synapses are often viewed as comprised solely of neuronal gap junction channels that allow direct ionic and metabolic communication. However, associated with the gap junction channels are structures observed by electron microscopy called the Electrical Synapse Density (ESD). The ESD has been suggested to be critical for the formation and function of the electrical synapse, yet the biochemical makeup of these structures is poorly understood. Here we find that electrical synapse formation in vivo requires an intracellular scaffold called Tight Junction Protein 1b (Tjp1b). Tjp1b is localized to electrical synapses where it is required for the stabilization of the gap junction channels and for electrical synapse function. Strikingly, we find that Tjp1b protein localizes and functions asymmetrically, exclusively on the postsynaptic side of the synapse. Our findings support a novel model in which there is molecular asymmetry at the level of the intracellular scaffold that is required for building the electrical synapse. ESD molecular asymmetries may be a fundamental motif of all nervous systems and could support functional asymmetry at the electrical synapse.

neuroscience↗