Biology subjects

Harris, S. N.

Publications and source records attributed to Harris, S. N..

3 recordsLinked to original sources

bioRxiv2026

Olfactory Loss Enhances Visual Learning in Drosophila through Structural and Functional Reorganisation

Loss of a sensory modality can enhance performance in the remaining senses. However, the circuit mechanisms by which such cross-modal compensation can improve cognitive functions, including learning, are unknown. Here, we show that compromising olfaction in both larval and adult Drosophila enhances visual associative learning. Using behavioural analysis, functional imaging, and comparative connectomics, we reveal the circuit mechanisms that underlie this improvement. Animals with improved learning ability have enhanced responses to visual stimuli in the higher-order learning circuit. The complementary circuit mechanisms that can enhance these responses are structural reweighting of inputs in the larva, resulting in an increased fraction of synaptic inputs from visual pathways onto neurons in the learning circuit, and a reduction in cross-modal inhibition in the adult. Together, these findings reveal synaptic and disinhibitory circuit mechanisms that enhance learning in higher-order associative networks following sensory loss.

neuroscience↗

bioRxiv2025

Descending neurons integrate learnt information from mushroom body with context to promote escape behaviour

To behave adaptively in the environment and select appropriate responses to sensory stimuli, animals integrate learnt information about the valences of stimuli with contextual information. While significant progress has been made in understanding how animals learn which stimuli predict positive and negative outcomes, how the outputs of associative learning circuits flexibly promote different behaviours, depending on context, is not well understood. Addressing this question requires mapping the pathways from learning circuits to nerve cord command neurons that promote specific actions, and understanding where and how contextual information converges with these pathways to modulate their activity. These are daunting tasks in larger brains where synaptic-resolution connectivity maps are not available. We, therefore, addressed this question in the tractable Drosophila larva using a combination of connectomic analyses, imaging and manipulation of neural activity and behavioural analysis. We characterised, with synaptic-resolution, the pathways from the higher-order learning circuit (the mushroom body, MB) all the way to a specific cord command neuron (Goro) in the nerve cord that promotes the most vigorous escape response, rolling. Rolling is the fastest, but also the most energetically costly escape response and is activated by multisensory cues in the context of predator attack. We identify a pair of brain descending neurons, Ipsigoro, that integrate learnt information (via input from MBONs) and nociceptive context (via input from ascending neurons) to facilitate rolling via direct inputs to Goro. Our study reveals the circuit mechanism by which context and learnt information are integrated by brain descending neurons to activate specific nerve cord command neurons and promote specific actions.

neuroscience↗

bioRxiv2018

Activity-dependent netrin-1 secretion drives synaptic insertion of GluA1-containing AMPA receptors in the hippocampus.

Dynamic trafficking of -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors (AMPARs) to synapses is critical for activity-dependent synaptic plasticity underlying learning and memory, however the identity of key molecular effectors remains elusive. Here, we demonstrate that membrane depolarization and N-methyl-D-aspartate receptor (NMDAR) activation triggers secretion of the chemotropic guidance cue netrin-1 from dendrites. Using selective genetic deletion, we show that netrin-1 expression by excitatory neurons is required for NMDAR-dependent long-term potentiation (LTP) in the adult hippocampus. Further, we demonstrate that application of exogenous netrin-1 is sufficient to trigger the potentiation of excitatory glutamatergic transmission at hippocampal Schaffer collateral synapses via Ca2+-dependent recruitment of GluA1-containing AMPARs, promoting the maturation of immature or nascent synapses. These findings identify a central role for activity-dependent release of netrin-1 as a critical effector of synaptic plasticity in the adult hippocampus.

neuroscience↗