Biology subjects

Burke, A. T.

Publications and source records attributed to Burke, A. T..

5 recordsLinked to original sources

bioRxiv2026

Uncovering Sex Differences in the Drosophila Ventral Nerve Cord Through Connectome Alignment

There are now multiple Drosophila connectomes available, comprising both its brain and spinal cord - comparing these connectomes requires first classifying neurons into cell types. Existing approaches for cell typing typically require extensive manual curation. Here we present a new method that automatically aligns connectomes via network topology alone. Using two complete male ventral nerve cord (VNC) connectomes as references, we assign cell types to [~]13,000 neurons intrinsic to the female VNC, and automatically identify sex-specific and sexually dimorphic cell types. We not only provide a comprehensive census of cell types across male and female nerve cords, but we uncover connectivity differences that underlie differences in function. We focus on circuits underlying song production in males and oviposition behaviors in females, and investigate the counterparts of these circuits across sexes. Our automated methods and analyses provide insights into sex differences in circuits that connect the brain and body, and pave the way for comparative connectomics at scale.

neuroscience↗

bioRxiv2025

New Synapse Detection in the Whole-Brain Connectome of Drosophila

The FlyWire Drosophila brain connectome1 is a graph of roughly 140K neurons and >50 million synaptic connections2,3 reconstructed from the FAFB EM dataset4. Challenges in synapse detection were identified for neurons with features such as dark cytosols, axo-axonic synapses, and complex polyadic synapses, due to limitations in ground truth data for these cells and the inherent complexity of these synapse types. To address these issues, we trained new neural networks using iteratively generated ground truth annotations and detected synapses across the entire FAFB dataset, producing what we refer to here as the Princeton synapses. These synapses were evaluated in both control regions, such as subareas of the mushroom body calyx and lateral horn, which were also chosen by Buhmann et al.3 for evaluation, as well as challenging regions, including Johnstons Organ neurons (JONs), photoreceptors, and other cell types. The new model shows significant improvements, achieving up to a 0.23 F-score increase in challenging areas, while maintaining performance in control regions. Princeton synapses also show an 8-9% improvement in neuron clustering within cell types and better left/right symmetry scores, especially for photoreceptors. Additionally, neuron type membership can be predicted from connectivity patterns alone with weighted F-scores of 0.93 for Princeton synapses versus 0.91 for Buhmann synapses. The updated Princeton synapses are now accessible via Codex (codex.flywire.ai).

neuroscience↗

bioRxiv2023

Sex- and age-dependent effects of locus coeruleus-originated tau dysfunction on olfaction and neurophysiology in rats

Braak and colleagues (2011) described human pretangle stages of abnormal tau protein originating in the locus coeruleus (LC) of young adults (Braaks Stages a-c, 1a-b), decades prior to the neurofibrillary tangle stages observed in Alzheimers disease. To capture the features of LC-originated pretangle tau stages, we used a rat model where male and female TH-Cre+/- rats received bilateral LC infusions of a hyperphosphorylated human tau (htauE14) gene via a viral vector. To assess the effects of age and sex on pretangle stage tau, we assayed physiological and behavioural changes 1-3mo (young) and 12+mo (aged) post LC-infusion (p.i.). Open field measures revealed age and sex-dependent differences in anxiety in LC-htauE14 infused rats and overall sex- and age-dependent differences in activity. Odour discrimination tests showed little impairment in LC-htauE14 infused rats at 1-3mo after LC infusion. At 12+mo p.i. however, LC-htauE14 male rats failed a difficult odour discrimination test and a further olfactory detection test (habituation-dishabituation), but male LC-Control rats and female rats were not impaired. LC neuronal firing rates were assessed in urethane-anesthetized aged (12+mo p.i.) male LC-htauE14 and LC-Control rats. The baseline level of firing of LC neurons in LC-htauE14 rats was higher than firing rates of LC-Control rats. Oscillatory patterns in LC firing were increased in amplitude and frequency by LC-htauE14. PSD95 density measures in piriform cortex were similar for LC-Control and LC-htauE14 male and female rats of young and aged groups. While synaptophysin density was higher in controls of the 1-3mo p.i. groups than in the LC-htauE14 rats, levels did not differ among aged groups. The increased excitability of LC cells observed may occur in relation to reduced LC axon arbours or may reflect a separate effect of htauE14 in LC neurons. The association of increased tonic LC activity to behavioural changes in the pretangle tau rat model merits further investigation.

neuroscience↗

bioRxiv2022

Sprague-Dawley rats differ in responses to medial perforant path paired pulse and tetanic activation as a function of sex and age

Network plasticity in the medial perforant path (MPP) of adult (5-9 mo) and aged (18-20 mo) urethane-anesthetized male and female Sprague-Dawley rats was characterized. Paired pulses probed recurrent networks before and after a moderate tetanic protocol. Adult females exhibited greater EPSP-spike coupling suggesting greater intrinsic excitability than adult males. Aged rats did not differ in EPSP-spike coupling but aged females had larger spikes at high currents than males. Paired pulses suggested lower GABA-B inhibition in females. Absolute population spike measures were larger post-tetani in female rats than male rats. Relative population spike increases were greatest in adult males relative to females and to aged males. EPSP slope potentiation was detected with normalization in some post-tetanic intervals for all groups except aged males. Tetani shortened spike latency across groups. Tetani-associated NMDA-mediated burst depolarizations were larger for the first two trains in each tetanus in adult males than other groups. EPSP slopes over 30 min post-tetani predicted spike size in female rats, but not in males. Replicating newer evidence MPP plasticity in adult males was mediated by increased intrinsic excitability. Female MPP plasticity was related to synaptic drive increases, not excitability increases. Aged male rats were deficient in MPP plasticity.

neuroscience↗

bioRxiv2020

The Neural Basis for a Persistent Internal State in Drosophila Females

Sustained changes in mood or action require persistent changes in neural activity, but it has been difficult to identify and characterize the neural circuit mechanisms that underlie persistent activity and contribute to long-lasting changes in behavior. Here, we focus on changes in the behavioral state of Drosophila females that persist for minutes following optogenetic activation of a single class of central brain neurons termed pC1. We find that female pC1 neurons drive a variety of persistent behaviors in the presence of males, including increased receptivity, shoving, and chasing. By reconstructing cells in a volume electron microscopic image of the female brain, we classify 7 different pC1 cell types and, using cell type specific driver lines, determine that one of these, pC1-Alpha, is responsible for driving persistent female shoving and chasing. Using calcium imaging, we locate sites of minutes-long persistent neural activity in the brain, which include pC1 neurons themselves. Finally, we exhaustively reconstruct all synaptic partners of a single pC1-Alpha neuron, and find recurrent connectivity that could support the persistent neural activity. Our work thus links minutes-long persistent changes in behavior with persistent neural activity and recurrent circuit architecture in the female brain.

neuroscience↗