Young Investigator
Talks
YIT | 1 | 04/10 - 18:00 | Aula Magna
Hot spot sites for alpha-synuclein amyloid assembly: a NMR and cryo-EM based study
Phelippe do Carmo Gonçalves
Max Planck Laboratory for Structural Biology, Chemistry and Molecular Biophysics of Rosario (MPLbioR, UNR-MPINAT).
Abstract
Misfolding and aberrant aggregation of alpha-synuclein (αS) is associated with neurological disorders collectively referred to as synucleinopathies. Current therapies for these disorders are limited and, therefore, understanding the mechanism of amyloid formation and its inhibition is of high clinical importance. The design of molecular probes that efficiently modulate the aggregation process and/or neutralize its associated toxicity constitutes a promising tool to enhance the understanding of the molecular mechanisms of αS assembly and for development of therapeutic strategies against these disorders. By combination of NMR and cryo-EM we performed a detailed structural characterization of specific αS interactions with a molecular probe along the aggregation landscape of the protein. Our results demonstrate that these interactions affect the kinetics of amyloid fibril formation of αS, modulating the structural features of the fibrils formed and leading to different αS polymorphs. By using a well-established cell-based bioassay our results indicate that these interactions can not only alter the structure but also the pathology of the resulting αS fibrils. Overall, our findings indicate that identification of hot spot interactions between αS and molecular probes may represent a viable alternative to design therapeutic molecules for the treatment of synucleinopathies.
YIT | 2 | 04/10 - 18:00 | Aula Magna
Profiling peripheral glial cells from human nerves for grafting in the CNS
Gabriela Aparicio
University of Kentucky
Abstract
The regenerative capability of PNS cells, including Schwann cells (SCs) has been exploited
clinically in cell transplantation therapies to treat CNS trauma and neurodegenerative diseases.
However, the characteristics of peripheral nerve cells has not yet been addressed thoroughly in
humans. The goal of this study was to identify specific markers able to reveal the identity and stage of differentiation of cells from intact and injured human nerves. Therefore, we developed and validated an in vitro model of human nerve degeneration to be compared with injured nerves from participants enrolled in a nerve transplantation clinical trial for Parkinson’s disease.
Histological analysis revealed that: (1) NGFR was a reliable marker to discriminate PNS cells from CNS neurons and glial cells; (2) S100B, GFAP and Sox10 were useful to specifically identify SCs
within nerve tissues, with the caveat that they also revealed glial populations in the CNS; and (3) MPZ and PRX were equally useful to identify myelin sheaths derived from SCs rather than oligodendrocytes. To conclude, these markers can be used in different combinations to reveal
grafted PNS cells, mainly SCs, in the human CNS to study their survival, differentiation and
relationship to host tissue.
Aparicio, Quintero, …, and Monje, (2024). J. Peripher. Nerv Syst. DOI:10.1111/jns.12643.
Aparicio & Monje (2023). Bio Protocol. 20;13(22): e4748. DOI: 10.21769/BioProtoc.4748.
YIT | 3 | 04/10 - 18:00 | Aula Magna
Interplay Between Early Nutritional Programming and Adult Obesogenic Diet on Brain Control of Food Intake
Pamela Fernández
Facultad de Bioquímica y Ciencias Biológicas (FBCB), Instituto de Salud y Ambiente del Litoral (ISAL), Universidad Nacional del Litoral (UNL), Santa Fe
Abstract
YIT | 4 | 04/10 - 18:00 | Aula Magna
Essential but implicit: the role of aging information in neurodegeneration detection
Fermín Travi
Facultad de Ciencias Exactas y Naturales - UBA
Abstract
A widespread hypothesis in brain imaging posits that neurodegenerative disorders constitute premature aging. Despite its prominence, this brain aging hypothesis (BAH) has not been verified against suitable alternatives. In this work, we first test a key assumption of BAH: Age information is necessary for detecting Alzheimer’s Disease (AD). We compared brain representations that were maximally uninformed about chronological age against ones that were maximally informed about age. We found that absence of aging information impairs AD detection, providing causal evidence for BAH.
Second, we investigated whether explicit age modeling confers advantages in
transfer learning for AD detection. We evaluated pretraining strategies for age, sex, and BMI inference and found that while pretraining improved representation stability and quality, these tasks converged to similar learned representations with no single phenotype providing superior advantage for neurodegeneration detection. These findings demonstrate that aging and neurodegeneration are fundamentally linked, yet aging information emerges naturally during
learning of brain features without dedicated encoding. This moves current thinking past brain-age gap conceptualizations and suggests new directions for foundation models integrating richer phenotypic information.
1° Facultad de Ciencias Exactas y Naturales, Departamento de Ciencias de la Computación, Universidad de Buenos Aires, Buenos Aires, Argentina
2° Laboratorio de Inteligencia Artificial Aplicada (LIAA), CONICET – Universidad de Buenos Aires, Instituto en Ciencias de la Computación (ICC), Buenos Aires, Argentina
3° IBM T. J. Watson Research Center, Yorktown Heights, New York, NY, United States
YIT | 5 | 04/10 - 18:00 | Aula Magna
Postnatal fluoxetine modulates the mouse prefrontal emotional circuit development
Tamara Adjimann
Instituto de Fisiología, Biología Molecular y Neurociencias, IFIBYNE (UBA-CONICET)
Abstract
Depression and anxiety are leading causes of disability worldwide, yet their developmental origins remain unclear. To explore early mechanisms of vulnerability to psychiatric disorders, we used a mouse model of adult emotional vulnerability induced by the early postnatal exposure to the antidepressant fluoxetine (FLX). C57BL/6 mice (both sexes) received FLX (10 mg/kg/day, p.o.) in 3% sucrose from postnatal day (P)2 to P14. At P15, we investigated the early impact on the prefrontal cortex-to-dorsal raphe nucleus (PFC-DRN) circuit, which is implicated in stress coping and mood regulation.
Using the high-resolution microscopy technique, Array Tomography, we observed a selective ~40% increase in glutamatergic PFC inputs to DRN serotonin (5-HT) neurons. Ex-vivo patch-clamp recordings supported the presence of additional functional glutamatergic synapses. Following acute stress in the forced swim test (FST), c-fos immunohistochemistry and layer-specific markers revealed heightened activation of specific PFC projection-neurons and increased 5-HT1A receptor-mediated inhibition in the DRN. Behaviorally, FLX-exposed mice showed reduced immobility in the FST, an effect reversed by 5-HT1A receptor blockade using the selective antagonist WAY-100635. Altogether, these findings reveal that postnatal FLX induces structural and functional remodeling of the nascent PFC-DRN circuit, likely contributing to altered stress responses and emotional behavior later in life.
YIT | 1 | 04/10 - 18:00 | Aula 5
Striatal cholinergic interneuron pause response requires Kv1 channels, is absent in dyskinetic mice, and is restored by dopamine D5 receptor inverse agonism
Cecilia Tubert
Laboratorio de Fisiología de Circuitos Neuronales, Grupo de Neurociencia de Sistemas, IFIBIO Houssay - UBA CONICET
Abstract
YIT | 2 | 04/10 - 18:00 | Aula 5
Glial GABA receptors control glia-neuron crosstalk in C. elegans
Melisa Lamberti
Universidad de Miami (UM), USA
Abstract
Gamma-amino butyric acid (GABA) is the most abundant inhibitory neurotransmitter in the brain. Normal GABA function requires specialized proteins such as biosynthetic enzymes, transporters and receptors. Defects in these proteins can lead to a specific imbalance of GABA neurotransmission and lead to diseases. Recent studies have shown that both GABAergic neurons and glia cells synthesize and release GABA to maintain neural excitatory-inhibitory balance, plasticity, neuroprotection, among other functions. Both neurons and glia cells express functional metabotropic and ionotropic GABA receptors, however, the role of these GABA receptors in the glia cells is still unknown. Probably the activation of these receptors in glia cells are important for neuron-glia interactions. Here, we use the powerful model organism C. elegans to uncover the function of GABA receptors expressed in the Amsh glia cell and how these regulate the neuron-glia interactions.
In particular, we focus on the study of GABAA receptors, UNC-49, LGC-36 and LGC-38, which are inhibitory chlorine-selective channels and how the activation of these receptors regulates the activity of Amsh glia and consequently the regulation of ASH neuron. We found that both GABA receptors in the Amsh glia affect the activity of these glia cells and the response to the octanol in the ASH neuron. In summary, our results show that UNC-49, LGC-36, and LGC-38 express in the Amsh glia could be an important role in the regulation of neuron-glia interaction.
YIT | 3 | 04/10 - 18:00 | Aula 5
Neural encoding reorganization through learning in the DG-CA3 circuit
Sol Ramos
IBIOBA
Abstract
The hippocampus is a brain region involved in memory and spatial navigation. The dentate gyrus
(DG), the first stage of hippocampal processing, sends information via mossy fibers to CA3 pyramidal neurons where it is integrated into a dense recurrent network. Yet, how these two hippocampal subfields encode information within the same task and how each restructures its
coding with experience remain unclear. In our study, we trained mice in a virtual reality discrimination task based on olfactory and visual context cues. We recorded DG and CA3 activity in first-session and expert animals using in vivo electrophysiology and quantified the contribution of sensory, behavioral, and cognitive variables to neuronal activity with a Poisson Generalized Linear Model. We observed that in the DG, the capacity of single neurons to respond to multiple variables simultaneously, known as mixed-selectivity, increases with learning. Moreover, encoding of position, speed, and reward strengthens, revealing experience-dependent reorganization. In contrast, CA3 exhibits mixed-selectivity even before learning, indicating an
intrinsic predisposition to integrate multiple signals. However, context, reward, and odors only become decodable in expert animals. These findings suggest that learning reorganizes DG and CA3 differently, enabling more specific encoding of key task elements. The DG builds its codes from experience, whereas CA3 refines and selects relevant signals on a preexisting framework.
YIT | 4 | 04/10 - 18:00 | Aula 5
Toward plug-and-play motor imagery-BCIs: Leveraging optimal
Catalina Galván
Instituto de Matemática aplicada del litoral, IMAL-CONICET-UNL
Abstract
Signal variability of electroencephalography-based computer interfaces (BCIs), especially in motor imagery (MI) paradigms used in rehabilitation, limits their use across subjects. Most MI-BCIs are trained using intra-subject data, leading to tedious calibration sessions for each user. Although inter-subject transfer learning strategies have been proposed, where large datasets are used to pretrain models, they still need substantial user data to perform the adaptation to yield sufficient performance for practical use.
I proposed cross-subject backward optimal transport (XS-BOT), a framework built on the principles of backward optimal transport for domain adaptation [1]. Using a model trained on a group of subjects, XS-BOT aligns the target subject’s data distribution with the source (training) data at the feature level, minimizing the amount of adaptation data and avoiding model retraining.
For both traditional machine learning [2] and deep learning [3] approaches, XS-BOT outperformed existing transfer learning methods by approximately 20 accuracy points, reaching over 80% with only 20 adaptation trials and data from just three EEG channels.
In summary, XS-BOT enables accurate cross-subject MI-BCI decoding with minimal calibration effort and simplified setup, which is crucial for rehabilitation use.
References:
[1] Peterson, V., et al. doi: 10.1109/TBME.2021.3105912.
[2] Blankertz B., et al. doi: 10.1109/MSP.2008.4408441.
[3] Lawhern, V. J., et al. doi: 10.1088/1741-2552/aace8c.
YIT | 5 | 04/10 - 18:00 | Aula 5
CIC-a deficiency induced neuronal and behavioral alterations in Drosophila melanogaster
Agustina Bruno-Vignolo
IBIOBA
Abstract
The circadian oscillator of Drosophila is comprised of approximately 150 clock neurons that express a set of molecular signatures, including clock genes, which through negative feedback loops coordinate oscillation of transcription and translation of other genes and proteins. A subgroup of clock neurons, called ventral lateral neurons (LNvs) is characterized by the expression of the neuropeptide Pigment Dispersing Factor (PDF). LNvs play a fundamental role in the control of alertness and are essential for the regulation of sleep/wake behavior via a yet not fully understood neuronal circuit. Previous work from our laboratory has identified ClC-a, a voltage-dependent chloride channel, as a potential key element in the physiological regulation of LNvs. This channel has not been explored in the Drosophila adult neurons. Therefore, the main objective of this project is to characterize the roles of neuronal CIC-a and its mechanism of action. Our findings indicate that downregulation of ClC-a in LNvs increases sleep in both female and male flies and reduces latency to siesta sleep. Additional behavioral analyses suggest that ClC-a may be involved in detection of sensory stimuli, such as light and mechanical stimuli. Based on these results, we performed electrophysiological recordings in the whole-cell patch clamp configuration. Our data indicate that ClC-a affects the physiology of LNvs, in agreement with our behavioral findings.