Biology subjects

Hige, T.

Publications and source records attributed to Hige, T..

6 recordsLinked to original sources

bioRxiv2025

Genetic and Circuit Mechanisms Underlying Natural Variation in Value-Based Decision Making

How natural regulatory genetic variation shapes innate economic decision biases by modifying neural circuit structure and function remains poorly understood. Here, we trace this pathway using a value-based oviposition decision in Drosophila. While laboratory flies reject sucrose in favor of a plain substrate, a wild-caught African strain accepts sucrose. This behavioral divergence maps to three African-specific intronic SNPs in the gene pumilio (pum), encoding an RNA-binding translational repressor. These SNPs downregulate pum, derepressing its target - the voltage-gated sodium channel paralytic (para) - in a pair of GABAergic interneurons that encode option values. Increased para enhances excitability, compresses neuronal value-coding differences between sucrose and plain options, and promotes sucrose acceptance. Selectively reducing pum or overexpressing para in these neurons converts laboratory flies to the African phenotype at physiological and behavioral levels. Our findings provide a genome-to-circuit-to-behavior model, illustrating how subtle regulatory polymorphisms reshape neural computations to drive adaptive variation in economic decision-making.

neuroscience↗

bioRxiv2023

A lightweight data-driven spiking neural network model of Drosophila olfactory nervous system with dedicated hardware support

Data-driven spiking neural network (SNN) models are vital for understanding the brains information processing at the cellular and synaptic level. While extensive research has focused on developing data-driven SNN models for mammalian brains, their complexity poses challenges in achieving precision. Network topology often relies on statistical inference, and the functions of specific brain regions and supporting neuronal activities remain unclear. Additionally, these models demand significant computational resources. Here, we propose a lightweight data-driven SNN model that strikes a balance between simplicity and reproducibility. We target the Drosophila olfactory nervous system, extracting its network topology from connectome data. The model implemented on an entry-level field-programmable gate array successfully reproduced the functions and characteristic spiking activities of different neuron types. Our approach thus provides a foundation for constructing lightweight in silico models that are critical for investigating the brains information processing mechanisms at the cellular and synaptic level through an analysis-by-construction approach and applicable to edge artificial intelligence (AI) systems.

neuroscience↗

bioRxiv2023

Cyclic nucleotide-induced bidirectional long-term synaptic plasticity in Drosophila mushroom body

Activation of the cAMP pathway is one of the common mechanisms underlying long-term potentiation (LTP). In the Drosophila mushroom body, simultaneous activation of odor-coding Kenyon cells (KCs) and reinforcement-coding dopaminergic neurons activates adenylyl cyclase in KC presynaptic terminals, which is believed to trigger synaptic plasticity underlying olfactory associative learning. However, learning induces long-term depression (LTD) at these synapses, contradicting the universal role of cAMP as a facilitator of transmission. Here, we develop a system to electrophysiologically monitor both short-term and long-term synaptic plasticity at KC output synapses and demonstrate that they are indeed an exception where activation of the cAMP/protein kinase A pathway induces LTD. Contrary to the prevailing model, our cAMP imaging finds no evidence for synergistic action of dopamine and KC activity on cAMP synthesis. Furthermore, we find that forskolin-induced cAMP increase alone is insufficient for plasticity induction; it additionally requires simultaneous KC activation to replicate the presynaptic LTD induced by pairing with dopamine. On the other hand, activation of the cGMP pathway paired with KC activation induces slowly developing LTP, proving antagonistic actions of the two second-messenger pathways predicted by behavioral study. Finally, KC subtype-specific interrogation of synapses reveals that different KC subtypes exhibit distinct plasticity duration even among synapses on the same postsynaptic neuron. Thus, our work not only revises the role of cAMP in synaptic plasticity by uncovering the unexpected convergence point of the cAMP pathway and neuronal activity, but also establishes the methods to address physiological mechanisms of synaptic plasticity in this important model. Abstract FigureMushroom body (MB) is the olfactory learning center of the Drosophila brain (left). Dopamine input activates the cAMP/Protein kinase A pathway in Kenyon cells (KCs), the principal neurons of the MB. When it coincides with KC activity, it induces presynaptic long-term depression at the synapses on the MB output neuron (Top right). A subset of dopaminergic neurons is also known to release nitric oxide, which activates the cGMP pathway. When it coincides with KC activity, it induces long-term potentiation (Bottom right). Created with BioRender.com.

neuroscience↗

bioRxiv2022

Neural circuit mechanisms for transforming learned olfactory valences into wind-oriented movement

How memories are used by the brain to guide future action is poorly understood. In olfactory associative learning in Drosophila, multiple compartments of the mushroom body act in parallel to assign valence to a stimulus. Here, we show that appetitive memories stored in different compartments induce different levels of upwind locomotion. Using a photoactivation screen of a new collection of split-GAL4 drivers and EM connectomics, we identified a cluster of neurons postsynaptic to the mushroom body output neurons (MBONs) that can trigger robust upwind steering. These UpWind Neurons (UpWiNs) integrate inhibitory and excitatory synaptic inputs from MBONs of appetitive and aversive memory compartments, respectively. After training, disinhibition from the appetitive-memory MBONs enhances the response of UpWiNs to reward-predicting odors. Blocking UpWiNs impaired appetitive memory and reduced upwind locomotion during retrieval. Photoactivation of UpWiNs also increased the chance of returning to a location where activation was initiated, suggesting an additional role in olfactory navigation. Thus, our results provide insight into how learned abstract valences are gradually transformed into concrete memory-driven actions through divergent and convergent networks, a neuronal architecture that is commonly found in the vertebrate and invertebrate brains.

neuroscience↗

bioRxiv2022

Lateral Axonal Modulation is Required for Stimulus-Specific Olfactory Conditioning in Drosophila

Effective and stimulus-specific learning is essential for animals survival. Two major mechanisms are known to aid stimulus-specificity of associative learning. One is accurate stimulus-specific representations in neurons. The second is limited effective temporal window for the reinforcing signals to induce neuromodulation only after sensory stimuli. However, these mechanisms are often imperfect in preventing unspecific associations; different sensory stimuli can be represented by overlapping populations of neurons, and more importantly the reinforcing signals alone can induce neuromodulation even without coincident sensory-evoked neuronal activity. Here, we report a crucial neuromodulatory mechanism that counteracts both limitations and is thereby essential for stimulus specificity of learning. In Drosophila, olfactory signals are sparsely represented by cholinergic Kenyon cells (KCs), which receive dopaminergic reinforcing input. We find that KCs have numerous axo-axonic connections mediated by the muscarinic type-B receptor (mAChR-B). By using functional imaging and optogenetic approaches, we show that these axo-axonic connections suppress both odor-evoked calcium responses and dopamine-evoked cAMP signals in neighboring KCs. Strikingly, behavior experiments demonstrate that mAChR-B knockdown in KCs impairs olfactory learning by inducing undesired changes to the valence of an odor that was not associated with the reinforcer. Thus, this local neuromodulation acts in concert with sparse sensory representations and global dopaminergic modulation to achieve effective and accurate memory formation. HighlightsO_LILateral KC axo-axonic connections are mediated by muscarinic type-B receptor C_LIO_LIKC connections suppress odor-evoked calcium responses and dopamine-evoked cAMP C_LIO_LIknockdown of the muscarinic type-B receptor impairs olfactory learning C_LIO_LIImpaired learning is due to changes to the valence of the unconditioned odor C_LI

neuroscience↗

bioRxiv2022

Hierarchical architecture of dopaminergic circuits enables second-order conditioning in Drosophila

Dopaminergic neurons with distinct projection patterns and physiological properties compose memory subsystems in a brain. However, it is poorly understood whether or how they interact during complex learning. Here, we identify a feedforward circuit formed between dopamine subsystems and show that it is essential for second-order conditioning, an ethologically important form of higher-order associative learning. The Drosophila mushroom body comprises a series of dopaminergic compartments, each of which exhibits distinct memory dynamics. We find that a slow and stable memory compartment can serve as an effective "teacher" by instructing other faster and transient memory compartments via a single key interneuron, which we identify by connectome analysis and neurotransmitter prediction. This excitatory interneuron acquires enhanced response to reward-predicting odor after first-order conditioning and, upon activation, evokes dopamine release in the "student" compartments. These hierarchical connections between dopamine subsystems explain distinct properties of first- and second-order memory long known by behavioral psychologists.

neuroscience↗