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After my doctorate, I made a postdoctoral fellowship (1992-1995) at the Eaton Peabody Laboratory (Harvard Medical School / Massachusetts Eye & Ear Infirmary, Boston, MA), where I completed my training as an electron microscopist. I later joined J. Defelipes lab at the Cajal Institute (Madrid, Spain) as a visiting researcher and served as an associate professor in different universities. During this period, I began my studies on the structure of the cerebral cortex and I further specialized in electron microscopy. I have recently contributed to the development of several methods for the study of the cerebral cortex using combined focused ion beam milling and scanning electron microscopy (FIB-SEM). These techniques facilitate the three-dimensional reconstruction of the ultrastructure of brain tissue and have been applied for the study of the densities and distributions of synapses in the cerebral cortex of the rat, mouse and Human. I have also participated in the development of software and image-analysis techniques. I am currently involved in the Cajal Blue Brain Project and in the Human Brain Project, where I collaborate with an interdisciplinary team of researchers in Spain and abroad.
Publications
1. Ultrastructure of the brain. Conventional transmission electron microscopy (TEM) and serial-section TEM with 3D reconstruction and quantitative analysis.
Merchán-Pérez, A., Rodriguez, J.-R., Ribak, C. E., and DeFelipe, J. (2009). Proximity of excitatory and inhibitory axon terminals adjacent to pyramidal cell bodies provides a putative basis for nonsynaptic interactions. Proc. Natl. Acad. Sci. U.S.A 106, 9878?9883. doi:10.1073/pnas.0900330106.
DeFelipe, J., Arellano, J. I., Merchán-Pérez, A., González-Albo, M. C., Walton, K., and Llinás, R. (2002). Spaceflight induces changes in the synaptic circuitry of the postnatal developing neocortex. Cerebral Cortex 12, 883?891. doi:10.1093/cercor/12.8.883.
Cossart, R., Dinocourt, C., Hirsch, J. C., Merchan-Perez, A., De Felipe, J., Ben-Ari, Y., et al. (2001). Dendritic but not somatic GABAergic inhibition is decreased in experimental epilepsy. Nature Neuroscience 4, 52?62. doi:10.1038/82900.
Hirsch, J. C., Agassandian, C., Merchán-Pérez, A., Ben-Ari, Y., DeFelipe, J., Esclapez, M., et al. (1999). Deficit of quantal release of GABA in experimental models of temporal lobe epilepsy. Nature Neuroscience 2, 499?500. doi:10.1038/9142.
2. Study of cortical connectivity using focused ion beam milling and scanning electron microscopy (FIB-SEM).
Luján R, Merchán-Pérez A, Soriano J, Martín-Belmonte A, Aguado C, Alfaro-Ruiz R, et al. Neuron Class and Target Variability in the Three-Dimensional Localization of SK2 Channels in Hippocampal Neurons as Detected by Immunogold FIB-SEM. Front Neuroanat (2021)15.
Eltokhi A, Santuy A, Merchan-Perez A, Sprengel R. Glutamatergic dysfunction and synaptic ultrastructural alterations in schizophrenia and autism spectrum disorder: Evidence from human and rodent studies. Int J Mol Sci (2021) 22(1):1-26.
Santuy A, Tomás-Roca L, Rodríguez J-, González-Soriano J, Zhu F, Qiu Z, et al. Estimation of the number of synapses in the hippocampus and brain-wide by volume electron microscopy and genetic labeling. Scientific Reports (2020)10(1).
Kikuchi T, Gonzalez-Soriano J, Kastanauskaite A, Benavides-Piccione R, Merchan-Perez A, Defelipe J, et al. Volume Electron Microscopy Study of the Relationship between Synapses and Astrocytes in the Developing Rat Somatosensory Cortex. Cereb Cortex (2020) 30(6):3800-3819.
Rodriguez-Moreno J, Porrero C, Rollenhagen A, Rubio-Teves M, Casas-Torremocha D, Alonso-Nanclares L, et al. Area-specific synapse structure in branched posterior nucleus axons reveals a new level of complexity in thalamocortical networks. J Neurosci (2020) 40(13):2663-2679.
Turegano-Lopez M, Santuy A, Defelipe J, Merchan-Perez A. Size, Shape, and Distribution of Multivesicular Bodies in the Juvenile Rat Somatosensory Cortex: A 3D Electron Microscopy Study. Cereb Cortex (2020) 30(3):1887-1901.
Kwon T, Merchán-Pérez A, Rial Verde EM, Rodríguez J-, Defelipe J, Yuste R. Ultrastructural, Molecular and Functional Mapping of GABAergic Synapses on Dendritic Spines and Shafts of Neocortical Pyramidal Neurons. Cereb Cortex (2019) 29(7):2771-2781.
Rodriguez-Moreno J, Rollenhagen A, Arlandis J, Santuy A, Merchan-Pérez A, DeFelipe J, et al. Quantitative 3D ultrastructure of thalamocortical synapses from the \"lemniscal\" ventral posteromedial nucleus in mouse barrel cortex. Cereb Cortex (2018) 28(9):3159-3175.
Santuy, A., Rodriguez, J. R., DeFelipe, J., and Merchan-Perez, A. (2018). Volume electron microscopy of the distribution of synapses in the neuropil of the juvenile rat somatosensory cortex. Brain Struct Funct 223, 77?90. doi:10.1007/s00429-017-1470-7.
Santuy, A., Rodríguez, J.-R., DeFelipe, J., and Merchán-Pérez, A. (2018). Study of the Size and Shape of Synapses in the Juvenile Rat Somatosensory Cortex with 3D Electron Microscopy. eNeuro 5. doi:10.1523/ENEURO.0377-17.2017.
Santuy, A., Turégano-López, M., Rodríguez, J. R., Alonso-Nanclares, L., DeFelipe, J., and Merchán-Pérez, A. (2018). A Quantitative Study on the Distribution of Mitochondria in the Neuropil of the Juvenile Rat Somatosensory Cortex. Cerebral Cortex 28, 3673?3684. doi:10.1093/cercor/bhy159.
Blazquez-Llorca, L., Valero-Freitag, S., Rodrigues, E. F., Merchán-Pérez, Á., Rodríguez, J. R., Dorostkar, M. M., et al. (2017). High plasticity of axonal pathology in Alzheimers disease mouse models. Acta Neuropathol Commun 5, 14. doi:10.1186/s40478-017-0415-y.
Merchán-Pérez, A., Rodríguez, J.-R., González, S., Robles, V., Defelipe, J., Larrañaga, P., et al. (2014). Three-dimensional spatial distribution of synapses in the neocortex: a dual-beam electron microscopy study. Cerebral Cortex 24, 1579?1588. doi:10.1093/cercor/bht018.
Blazquez-Llorca, L., Merchán-Pérez, A., Rodríguez, J.-R., Gascón, J., and Defelipe, J. (2013). FIB/SEM Technology and Alzheimers Disease: Three-Dimensional Analysis of Human Cortical Synapses. J. Alzheimers Dis. 34, 995?1013. doi:10.3233/JAD-122038.
Merchán-Pérez, A., Rodriguez, J.-R., Alonso-Nanclares, L., Schertel, A., and Defelipe, J. (2009). Counting synapses using FIB/SEM microscopy: a true revolution for ultrastructural volume reconstruction. Front Neuroanat 3, 18. doi:10.3389/neuro.05.018.2009.
3. Development of software, image-analysis techniques and improved electron microscopy methods.
Turegano-Lopez M, Santuy A, Kastanauskaite A, Rodriguez J-, DeFelipe J, Merchan-Perez A. Single-Neuron Labeling in Fixed Tissue and Targeted Volume Electron Microscopy. Front Neuroanat (2022)16.
Turégano-López M, Rodríguez J-, Alonso-Nanclares L, González-Soriano J, DeFelipe J, Merchán-Pérez A. Pre-Embedding Immunostaining of Brain Tissue and Three-Dimensional Imaging with FIB-SEM. Neuromethods (2021) 169:285-302.
Rodríguez, J.-R., Turégano-López, M., DeFelipe, J., and Merchán-Pérez, A. (2018). Neuroanatomy from Mesoscopic to Nanoscopic Scales: An Improved Method for the Observation of Semithin Sections by High-Resolution Scanning Electron Microscopy. Front. Neuroanat. 12. doi:10.3389/fnana.2018.00014.
Márquez Neila, P. M., Baumela, L., González-Soriano, J., Rodríguez, J.-R., DeFelipe, J., and Merchán-Pérez, Á. (2016). A Fast Method for the Segmentation of Synaptic Junctions and Mitochondria in Serial Electron Microscopic Images of the Brain. Neuroinformatics 14, 235?250. doi:10.1007/s12021-015-9288-z.
Morales, J., Rodríguez, A., Rodríguez, J.-R., DeFelipe, J., and Merchán-Pérez, A. (2013). Characterization and extraction of the synaptic apposition surface for synaptic geometry analysis. Front. Neuroanat 7, 20. doi:10.3389/fnana.2013.00020.
Morales, J., Alonso-Nanclares, L., Rodríguez, J.-R., DeFelipe, J., Rodríguez, Á., and Merchán-Pérez, A. (2011). Espina: a tool for the automated segmentation and counting of synapses in large stacks of electron microscopy images. Front. Neuroanat. 5, 18. doi:10.3389/fnana.2011.00018.
4. Other publications can be found at:
https://orcid.org/0000-0002-7228-5821
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