Biology subjects

Escribano, B.

Publications and source records attributed to Escribano, B..

5 recordsLinked to original sources

bioRxiv2026

A low-adhesion mechanism enables axon growth in the developing brain

During development, axons grow through complex tissue environments to wire the brain. Axon growth speeds measured in cell culture are incompatible with the distances axons must cover in vivo. Yet how axons achieve the growth speeds required to establish long-range connectivity within a narrow embryonic developmental window, and by what mechanism, remains unknown. Here, using long-term live imaging in brain sections, mouse genetics, molecular and pharmacological perturbations, together with AxoVivo, a newly developed intravital imaging platform that resolves subcellular structures, including growth cones and cytoskeletal dynamics, in living mouse embryos, we show that axons of cortical projection neurons (CPNs) employ a low-adhesion mechanism to grow. Even as growth cones change shape and turn, axons grow an order of magnitude faster than in vitro. The actin motor myosin II controls the growth cone actin cytoskeleton and its morphology but not axon growth itself, which is instead promoted by microtubule stabilisation. Finally, super-resolution shadow imaging (SUSHI) revealed that growth cones do not pull on the surrounding extracellular matrix. Taken together, this low-adhesion mechanism driven by protruding microtubules ensures the rapid growth necessary for long-distance wiring of the developing nervous system.

neuroscience↗

bioRxiv2026

Loss of NudE-mediated dynein activation at synaptic terminals causes progressive axon length-dependent neurodegeneration

Progressive, axon length-dependent degeneration of nerve terminals is a defining feature of dying-back neuropathies; yet, whether defects in axonal transport initiate or are a consequence of this process remains unresolved. Here, we show that NudE, a scaffold for dynein motor activation, is required for the initiation of retrograde axonal transport at Drosophila motoneuron synapses in vivo. Loss of NudE impairs dynein activation at the synaptic terminal, severely reducing the proportion of cargo entering retrograde transport and decreasing retrograde motor velocity. Live imaging and temporal analysis establish that this transport initiation defect is the earliest event in a degenerative cascade, followed by progressive microtubule destabilization, impaired synaptic transmission, and structural degeneration in a distal-to-proximal gradient that recapitulates dying-back neuropathies. Structure-function analysis validates the biochemically defined NudE-dynein binding domains in vivo, with graded disruption producing correspondingly graded phenotypes. Genetic two-hit experiments uncover a reciprocal dependence between transport initiation and microtubule maintenance: perturbations in either process that are individually tolerated synergistically trigger degeneration when combined, while increasing microtubule levels alone cannot compensate for failed dynein activation. These findings reveal retrograde transport initiation as a critical vulnerability point in motoneurons and provide a mechanistic basis for how defects in dynein activation produce progressive neurodegeneration.

neuroscience↗

bioRxiv2024

Heterogeneous plasticity of amygdala interneurons in associative learning and extinction

Neural circuits undergo experience-dependent plasticity to form long-lasting memories. Excitatory projection neurons are considered to be the primary neuronal substrate for memory acquisition and storage. However, inhibitory interneurons control the activity of projection neurons in a in a spatially and temporally precise manner, yet their contribution to memory acquisition, storage and expression remains poorly understood. Here, we employ a miniature microscope imaging approach to monitor the activity of large amygdala interneuron populations in freely moving mice during fear learning and extinction at the single cell level. We find that amygdala interneurons display mixed-selectivity and show complex plastic responses at both the ensemble and single neuron level across the acquisition, expression and extinction of aversive memories. In contrast to bidirectional single cell plasticity across distinct fear states, learning-induced changes at the population level occur transiently during conditioning and do not consolidate across days. Examining molecular interneuron subpopulations revealed that disinhibitory vasoactive intestinal peptide (VIP) expressing cells are predominantly activated by high fear states. In contrast, somatostatin (SST) interneurons display a preference for safety cues and thereby suppress excitatory neuron responsiveness. However, responses of individual neurons within the SST and VIP populations are non-uniform, indicating the presence of functional subtypes within classical molecularly-defined interneuron populations. Taken together, we identify complex neuronal plasticity within amygdala interneuron ensembles that goes beyond a passive processing function, suggesting a critical role of inhibitory microcircuit elements for memory selectivity and stability.

neuroscience↗

bioRxiv2020

Dendritic signal integration in Drosophila Mushroom Body Output Neuron (MBON) essential for learning and memory

The ability to associate neutral stimuli with valence information and to store these associations as memories forms the basis for decision making. To determine the underlying computational principles, we build a realistic computational model of a central decision module within the Drosophila mushroom body (MB), the flys center for learning and memory. Our model combines the electron microscopy-based architecture of one MB output neuron (MBON-3), the synaptic connectivity of its 948 presynaptic Kenyon cells (KCs), and its membrane properties obtained from patch-clamp recordings. We show that this neuron is electrotonically compact and that synaptic input corresponding to simulated odor input robustly drives its spiking behavior. Therefore, sparse innervation by KCs can efficiently control and modulate MBON activity in response to learning with minimal requirements on the specificity of synaptic localization. This architecture allows efficient storage of large numbers of memories using the flexible stochastic connectivity of the circuit.

neuroscience↗

bioRxiv2019

Integration of Odor-Induced Activity of Kenyon Cells in an Electrotonically Compact Drosophila Mushroom Body Output Neuron (MBON)

The formation of an ecologically useful lasting memory requires that the brain has an accurate internal representation of the surrounding environment. In addition, it must have the ability to integrate a variety of different sensory stimuli and associate them with rewarding and aversive behavioral outcomes. Over the previous years, a number of studies have dissected the anatomy and elucidated some of the working principles of the Drosophila mushroom body (MB), the flys center for learning and memory. As a consequence, we now have a functional understanding of where and how in the MB sensory stimuli converge and are associated. However, the molecular and cellular dynamics at the critical synaptic intersection for this process, the Kenyon cell-mushroom body output neuron (KC-MBON) synapse, are largely unknown. Here, we introduce a first approach to understand this integration process and the physiological changes occurring at the KC-MBON synapse during Kenyon cell (KC) activation. We use the published connectome of the Drosophila MB to construct a functional computational model of the MBON-3 dendritic structure. We simulate synaptic input by individual KC-MBON synapses by current injections into precisely (m) identified local dendritic sections, and the input from a model population of KCs representing an odor by a spatially distributed cluster of current injections. By recording the effect of the simulated current injections on the membrane potential of the neuron, we show that the MBON-3 is electrotonically compact. This suggests that odor-induced MBON activity is likely governed by input strength while the positions of KC input synapses are largely irrelevant.

neuroscience↗