Biology subjects

Boto, T.

Publications and source records attributed to Boto, T..

4 recordsLinked to original sources

bioRxiv2026

Modeling Post-traumatic memory deficits: Repeated head injury effects on Novelty detection in Drosophila

Traumatic brain injury (TBI) is a leading cause of neurological dysfunction, yet the mechanisms linking repeated concussions to cognitive impairment remain poorly defined. Here, we used a controlled Drosophila model of repetitive head trauma using a piezoelectric actuator to deliver reproducible mild, moderate, or severe concussions. Repeated trauma significantly reduced lifespan and induced transient locomotor deficits, persistent motivational impairments, and surprisingly sleep behavior was only altered with injury protocols expanding across more than one day. At the cellular level, concussions triggered a delayed but robust proliferation of astrocyte-like glia, consistent with neuroinflammatory responses observed in mammalian models. To investigate circuit-level consequences, we examined novelty detection within the mushroom body, focusing on MBON-3, a neuron that shows plasticity consistent with odor habituation similar to previously reported for MBON-3. Functional calcium imaging revealed that concussed flies exhibited disrupted odor-induced plasticity and diminished baseline responsiveness in MBON-3 at one- and five- days post-injury, despite intact Kenyon cell input. Notably, these deficits were force-dependent and largely reversible by ten days, highlighting both vulnerability and resilience within this defined circuit. Together, our findings demonstrate that repeated concussions in Drosophila produce dose-dependent behavioral, cellular, and circuit dysfunctions that parallel mammalian TBI. This work establishes a genetically tractable platform for dissecting the mechanisms of concussion-induced cognitive decline and for identifying potential targets for intervention.

neuroscience↗

bioRxiv2025

The Ataxin-2 protein is required in Kenyon cells for RNP-granule assembly and appetitive long-term memory formation.

Ribonucleo-protein granules (mRNP granules) are thought to contribute to the control of neuronal mRNA translation required for consolidation of long-term memories. Consistent with this, the function of Ataxin-2 in mRNA granule assembly has been shown to be required for long-term olfactory habituation (LTH) in Drosophila, a form of non-associative memory. Knockdown of Ataxin-2 in either local interneurons (LNs) or projection neurons (PNs) of the insect antennal lobe disrupts LTH, leading to a model in which Ataxin-dependent translational control is required in both presynaptic and postsynaptic elements of the LN-PN synapse, whose potentiation has been causally linked to LTH. Here we use novel and established methods for cell-type specific perturbation to ask: (a) whether Ataxin-2 controls mRNA granule assembly in cell types beyond the few that have been examined; and (b) whether it functions not only in LTH, but also for long-term olfactory associative memory (LTM). We show that Ataxin-2 controls mRNP granule assembly in additional neuronal types, namely Kenyon Cells that encode associative memory, as well as more broadly in non-neuronal cells, e.g. in nurse cells in the egg chamber. Furthermore, selective knockdown of Atx2 in /{beta} and /{beta} KCs blocks appetitive long-term but not short-term associative memories. Taken together these observations support a hypothesis that Ataxin-2 dependent translational control is widely required across different mnemonic circuits for consolidation of respective forms of long-term memories.

neuroscience↗

bioRxiv2021

Associative learning drives longitudinally-graded presynaptic plasticity of neurotransmitter release along axonal compartments

Anatomical and physiological compartmentalization of neurons is a mechanism to increase the computational capacity of a circuit, and a major question is what role axonal compartmentalization plays. Axonal compartmentalization may enable localized, presynaptic plasticity to alter neuronal output in a flexible, experience-dependent manner. Here we show that olfactory learning generates compartmentalized, bidirectional plasticity of acetylcholine release that varies across the longitudinal compartments of Drosophila mushroom body (MB) axons. The directionality of the learning-induced plasticity depends on the valence of the learning event (aversive vs. appetitive), varies linearly across proximal to distal compartments following appetitive conditioning, and correlates with learning-induced changes in downstream mushroom body output neurons (MBONs) that modulate behavioral action selection. Potentiation of acetylcholine release was dependent on the CaV2.1 calcium channel subunit cacophony. In addition, contrast between the positive conditioned stimulus and other odors required the inositol triphosphate receptor (IP3R), which was required to maintain responsivity to odors in untrained conditions. Downstream from the mushroom body, a set of MBONs that receive their input from the {gamma}3 MB compartment were required for normal appetitive learning, suggesting that they represent a key node through which discriminative effects influence appetitive memory and decision-making. These data demonstrate that learning drives valence-correlated, compartmentalized, bidirectional potentiation and depression of synaptic neurotransmitter release, which rely on distinct mechanisms and are distributed across axonal compartments in a learning circuit.

neuroscience↗

bioRxiv2019

Neurofibromin regulates metabolic rate via neuronal mechanisms in Drosophila

Neurofibromatosis type 1 (NF1) is a genetic disorder predisposing patients to a range of features, the most characteristic of which include areas of abnormal skin pigmentation and benign tumors associated with peripheral nerves, termed neurofibromas. Less common, but more serious symptoms also include malignant peripheral nerve sheath tumors, other malignancies, and learning disabilities. The NF1 gene encodes neurofibromin, a large protein that functions as a negative regulator of Ras signaling and mediates pleiotropic cellular and organismal function. Recent evidence suggests NF1 may regulate metabolism, though the mechanisms are unknown. Here we show that the Drosophila ortholog of NF1, dNf1 regulates metabolic homeostasis in fruit flies by functioning within a discrete brain circuit. Loss of dNf1 increases metabolic rate and feeding, enhances starvation susceptibility, and decreases lipid stores while increasing lipid turnover rate. The increase in metabolic rate is independent of locomotor activity (grooming), and maps to a subset of neurons in the ventral nervous system. The feeding and metabolic rate effects are due to loss of dNf1 in the same set of neurons, suggesting that increased feeding may be a compensatory effect driven by the increase in metabolic rate and lipid turnover. Finally, we show that the Ras GAP-related domain of neurofibromin is required for normal metabolism, demonstrating that Ras signaling downstream of dNf1 mediates the metabolic effects. These data demonstrate that dNf1 regulates metabolic rate via neuronal mechanisms, suggest that cellular and systemic metabolic alterations may represent a pathophysiological mechanism in NF1, and provide a platform for investigating the cellular role of neurofibromin in metabolic homeostasis.

neuroscience↗