Modulation of cofilin 1 phosphorylation induces juvenile-like plasticity in the adult mouse visual cortex

Neuroscience 2026 595:262-269

Agustina Dapueto 1 , Emilia Hayek 2 , Alejo Acuña 3 , Bruno Pannunzio 4 , Leonel Gomez 5 , Francesco M Rossi 6

1 Laboratorio de Neurociencias "Unidad de Neuroplasticidad", Instituto de Biología, Departamento de Biología Celular y Molecular, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay; Present address: Laboratorio de Mecanismos de Neurodegeneración y Neuroprotección, Departamento de Neuroquímica, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay. Electronic address: agustinadapueto@gmail.com. 2 Laboratorio de Neurociencias "Unidad de Neuroplasticidad", Instituto de Biología, Departamento de Biología Celular y Molecular, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay. Electronic address: hayekemilia03@gmail.com. 3 Laboratorio de Neurociencias "Unidad de Neuroplasticidad", Instituto de Biología, Departamento de Biología Celular y Molecular, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay. Electronic address: alejoacu@gmail.com. 4 Laboratorio de Neurociencias "Unidad de Neuroplasticidad", Instituto de Biología, Departamento de Biología Celular y Molecular, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay; Present address: Departamento de Histología y Embriología, Facultad de Medicina, UdelaR / Laboratorio de Neuroinflamación y Terapia Génica del Institut Pasteur de Montevideo, Uruguay. Electronic address: brunopannunzio@gmail.com. 5 Laboratorio de Neurociencias "Unidad de Neuroplasticidad", Instituto de Biología, Departamento de Biología Celular y Molecular, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay. Electronic address: leonel.gomez@gmail.com. 6 Laboratorio de Neurociencias "Unidad de Neuroplasticidad", Instituto de Biología, Departamento de Biología Celular y Molecular, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay. Electronic address: fmrossi@fcien.edu.uy.

DOI: 10.1016/j.neuroscience.2026.01.003
PMID: 41506312
Pubmed: https://pubmed.ncbi.nlm.nih.gov/41506312
Texto completo: https://www.sciencedirect.com/science/article/pii/S0306452226000035

Abstract:
Cofilin 1 is an actin-depolymerizing protein that plays a fundamental role in actin dynamics, particularly within dendritic spines, where it has been implicated in both structural and functional plasticity. We recently demonstrated, using a combination of differential proteomics, western blot and immunohistochemistry, that the expression of cofilin 1 and its inactive phosphorylated form is dynamically regulated in the mouse visual cortex. Expression levels change across critical periods of postnatal development and are modulated by visual experience, suggesting that cofilin 1 plays a dynamic role in synaptic remodeling during windows of heightened cortical plasticity. In this study, we sought to determine whether cofilin 1 influences experience-dependent plasticity in the adult visual cortex, a stage where plasticity is more restricted but still inducible under specific conditions. Specifically, we administered a synthetic peptide inhibitor of cofilin 1 activity in vivo (PCOF). Following monocular deprivation, adult mice received either the PCOF peptide or a control peptide. Structural plasticity was assessed by quantifying dendritic spine density using Golgi-like staining, while visual plasticity was evaluated by measuring visual acuity through the optomotor response test. Our results show that, in adult mice treated with the PCOF peptide - but not in controls - monocular deprivation led to a significant reduction in dendritic spine density in the contralateral visual cortex, as well as a decrease in visual acuity of the previously deprived eye. These findings indicate that cofilin 1 activity is crucial for the regulation of experience-dependent plasticity in the adult mouse visual cortex.

Environmental drivers of calling activity in a southern subtropical anuran assemblage: insights from passive acoustic monitoring

Bioacoustics 2026 35(1), 75–89

Pouso, P 1, Cabana, Á 2, Nieto Methol, C 1

1 Laboratorio Bases Neurales de la Comunicación Acústica, Unidad Académica de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay 2 CICADA and Instituto de Fundamentos y Métodos, Facultad de Psicología, Universidad de la República, Montevideo, Uruguay

DOI: 10.1080/09524622.2025.2597859
PMID:
Pubmed: https://pubmed.ncbi.nlm.nih.gov/
Texto completo: https://www.tandfonline.com/doi/full/10.1080/09524622.2025.2597859

Abstract:
In anurans, acoustic communication is a crucial reproductive behaviour shaped by individual traits, social interactions and environmental cues. External factors such as temperature, rainfall and photoperiod can elicit physiological responses that drive behavioural rhythms at individual and population scales. While temperature and rainfall effects on anuran calling activity are well-established, photoperiodic influences remain comparatively understudied, particularly within southern subtropical assemblages. We assessed hourly calling activity of Boana pulchella in Uruguay over a 12-month period using Passive Acoustic Monitoring (PAM) and validated semi-automated data processing methods to examine environmental drivers in a subtropical permanent pond. Calling behaviour increased during the warmer months, showing a clear seasonal pattern. Peak activity timing remained consistent across seasons, but the temporal window of vocalisations expanded during winter (long nights) and contracted during summer (long days), reflecting photoperiodic variation. Linear regression analyses showed significant effects of photoperiod, temperature and their interaction on calling activity, while rainfall and atmospheric pressure showed no effect. These findings underscore the regulatory role of photoperiod in shaping reproductive acoustic behaviour and highlight the need to further explore its physiological and adaptive significance, especially within underrepresented subtropical assemblages.

CD300f enables microglial damage sensing, efferocytosis, and apoptotic cell metabolization after brain injury

Brain Behav Immun 2025 130:106105

Luciana Negro-Demontel 1 , Frances Evans 2 , Fabio Andrés Cawen 3 , Zachary Fitzpatrick 4 , Hannah D Mason 4 , Daniela Alí-Ruiz 5 , Rubèn López-Vales 6 , Natalia Lago 6 , Hugo Peluffo 7

1 Department of Histology and Embriology, School of Medicine, UDELAR, Montevideo, 11800, Uruguay; Institut Pasteur de Montevideo, Montevideo, 11400, Uruguay; National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, MD, USA. Electronic address: Lucianan@wustl.edu. 2 Department of Histology and Embriology, School of Medicine, UDELAR, Montevideo, 11800, Uruguay; Institut Pasteur de Montevideo, Montevideo, 11400, Uruguay. 3 Institut Pasteur de Montevideo, Montevideo, 11400, Uruguay; Unitat de Bioquímica i Biologia Molecular, Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), 08036, Spain; Institut de Neurociències, Universitat de Barcelona (UB), 08036, Spain. 4 National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, MD, USA. 5 Institut Pasteur de Montevideo, Montevideo, 11400, Uruguay. 6 Departament de Biologia Cel·lular, Fisiologia i Immunologia, Universitat Autònoma de Barcelona (UAB), Spain; Institut de Neurociències, Autonomous University of Barcelona (UAB), Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain. 7 Institut Pasteur de Montevideo, Montevideo, 11400, Uruguay; Unitat de Bioquímica i Biologia Molecular, Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), 08036, Spain; Institut de Neurociències, Universitat de Barcelona (UB), 08036, Spain. Electronic address: hugo.peluffo@ub.edu.

DOI: 10.1016/j.bbi.2025.106105
PMID: 40935207
Pubmed: https://pubmed.ncbi.nlm.nih.gov/40935207
Texto completo: https://www.sciencedirect.com/science/article/pii/S0889159125003472?via%3Dihub

Abstract:
Microglia, the resident phagocytes of the central nervous system (CNS), continuously survey the parenchyma and its borders, acting as first responders to brain injury. Their ability to detect and react to environmental changes is mediated by a repertoire of surface receptors collectively known as themicroglial sensome. Here, we identify the lipid-sensing immunoreceptor CD300f as a key regulator of microglial responses to tissue damage and apoptotic cells. Using intravital two-photon microscopy, we show that CD300f-/- microglia fail to extend processes toward a laser-induced cortical lesion, indicating impaired detection of damage-associated cues. In models of mild traumatic brain injury (mTBI) and intracortical injection of apoptotic cells, CD300f deficiency led to reduced recognition and clearance of dying cells resulting in the accumulation of cellular debris within the parenchyma. At later stages, apoptotic remnants were retained within CD300f-/- microglia in vivo and bone marrow-derived macrophages in vitro, suggesting defective intracellular degradation. Proteomic analysis after a controlled cortical injury (CCI) contusion model revealed widespread dysregulation of autophagy-related and metabolic pathways, consistent with impaired efferocytosis and phagolysosomal processing. In parallel, we observed upregulation of the UDP-degrading ectonucleotidase ENTPD6 protein and downregulation of the microglial purinergic receptor P2ry6 mRNA, indicating a dysfunctional UDP-P2RY6 axis that may underlie impaired damage sensing and phagocytic initiation. Despite greater histological preservation, CD300f-/- mice exhibited worse long-term functional recovery after brain injury. Together, these findings highlight CD300f as a key damage-associated molecular pattern (DAMP) receptor that integrates purinergic signaling, efferocytosis, and metabolic adaptation, highlighting its essential role in coordinating microglial responses to CNS injury.

Pericyte pannexin1 controls cerebral capillary diameter and supports memory function

Nat Commun 2025 16(1):6128

Sandra Mai-Morente 1, Eugenia Isasi 2, Alberto Rafael 1, Gonzalo Budelli 3, Silvia Olivera-Bravo 4, Nathalia Vitureira 1, Verónica Abudara 1

1 Departamento de Fisiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay 2 Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay 3 Departamento de Biofísica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay 4 Departamento de Neurobiología y Neuropatología, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Montevideo, Uruguay

DOI: 10.1038/s41467-025-61312-0
PMID: 40610448
Pubmed: https://pubmed.ncbi.nlm.nih.gov/40610448
Texto completo: https://www.nature.com/articles/s41467-025-61312-0

Abstract:
In the blood-brain-barrier, contractile pericytes fine-tune the capillary resistance and blood supply to meet neuro-metabolic demands; molecular players governing these functions remain unclear. Here we show that mice cerebral pericytes express functional pannexin1 (Panx1) channels, which drive efflux of ATP, a key activator of pericyte contractility. In hippocampal slices, pericyte Panx1 mediates capillary diameter changes in response to extracellular ATP fluctuations and glutamatergic synaptic transmission, known to contribute functional hyperaemia. Pharmacological inhibition of Panx1 in mice induces capillary widening in the cortex and hippocampus. Genetic deletion of pericyte Panx1 disrupts learning-evoked capillary dilation and memory performance. Mechanistically, glutamatergic NMDA/AMPA and purinergic P2X7/P2Y6 receptors modulate pericyte Panx1 activity, which ultimately adjusts ATP release, pericyte Ca2+ signalling and capillary dynamics. Our study unveils pericyte Panx1 as a physiological regulator of cerebral capillary diameter, which sustains brain function and serves as a potential therapeutic target for cerebrovascular cognitive disorders.

Mai-Morente_2025_Pericyte pannexin1 controls cerebral capillary diameter and supports memory function.pdf