Cajal Blue Brain Platform CSIC/UPM

Research

One of the main goals of neuroscience is to understand the biological mechanisms responsible for human mental activity. In particular, the study of the cerebral cortex is and without any doubt will be the greatest challenge for science in the next centuries, since it represents the foundation of our humanity. In other words, the cerebral cortex is the structure whose activity is related to the capabilities that distinguish humans from other mammals. Thanks to the development and evolution of the cerebral cortex we are able to perform highly complex and specifically human tasks, such as writing a book, composing a symphony or developing technologies. For these reasons, the study of the normal brain is obviously necessary to better understand not only how our brain functions under normal conditions, but also how its alterations give rise to many devastating brain diseases like AD. Indeed, the Cajal Blue Brain node (CSIC/UPM) was created as a basic research unit located at the Montegancedo Campus (UPM, Madrid), as a continuation of the Cajal Blue Brain Project (https://cajalbbp.es/). The node is aimed to study the structural and functional organization of the human brain (both in health and disease) as well as the brain of  different experimental animals, coordinating different levels of analysis (molecules, synapses, neurons, local circuits, brain networks function and modelling). Also, a major objective of the node is to develop new techniques and strategies for studying brain structural organization and function.

Lines of investigation

1. High throughput brain-wide screening of morphological and neurochemical types of synapses and cells 

2. Detailed single cell studies using cell filling

3. Detailed synapse studies using 3D electron microscopy

4. Informatics and modelling

Team

Publications of the last 5 years

• León-Espinosa G, Regalado-Reyes M, DeFelipe J, Muñoz A (2018) Changes in neocortical and hippocampal microglial cells during hibernation. Brain Struct Funct. 223:1881–1895. https://doi.org/10.1007/s00429-017-1596-7
• Santuy A, Rodriguez JR, DeFelipe J, 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. https://doi.org/10.1007/s00429-017-1470-7
• Santuy A, Rodríguez JR, DeFelipe J, Merchán-Pérez A (2018) Study of the size and shape of synapses in the juvenile rat somatosensory cortex with 3D Electron Microscopy. eNeuro 5(1), ENEURO.0377-17.2017. https://doi.org/10.1523/eneuro.0377-17.2017
• Domínguez-Álvaro M,Montero-Crespo M, Blázquez-Llorca L, Insausti R, DeFelipe J, AlonsoNanclares L (2018) Three-dimensional analysis of synapses in the transentorhinal cortex of Alzheimer’s disease patients. Acta Neuropathol Commun. 6:20. https://doi.org/10.1186/s40478-018-0520-6
• 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. 12:14. https://doi.org/10.3389/fnana.2018.00014
• Varando G, Benavides-Piccione R, Muñoz A, Kastanauskaite A, Bielza C, Larrañaga P, DeFelipe J (2018) MultiMap: A tool to automatically extract and analyse spatial microscopic data from large stacks of confocal microscopy images. Front. Neuroanat. 12:37. https://doi.org/10.3389/fnana.2018.00037
• Luengo-Sanchez S, Fernaud-Espinosa I, Bielza C, Benavides-Piccione R, Larrañaga P, DeFelipe J (2018) 3D morphology-based clustering and simulation of human pyramidal cell dendritic spines. PLoS Comput Biol. 14(6):e1006221. https://doi.org/10.1371/journal.pcbi.1006221
• Furcila D, DeFelipe J, Alonso-Nanclares L (2018) A Study of Amyloid-β and Phosphotau in Plaques and Neurons in the Hippocampus of Alzheimer’s Disease Patients. J Alzheimers Dis. 64:417-435. https://doi.org/10.3233/jad-180173
• Fernández-Cabrera MR, Higuera-Matas A, Fernaud-Espinosa I, DeFelipe J, Ambrosio E, Miguéns  M (2018)Selective effects of Δ9-tetrahydrocannabinol on medium spiny neurons inthe striatum. PLoS One. https://doi.org/10.1371/journal.pone.0200950
• Eyal G, Verhoog MB, Testa-Silva G, Deitcher Y, Benavides-Piccione R, DeFelipe J, de Kock CPJ, Mansvelder HD, Segev I (2018) Human cortical pyramidal neurons: from spines to spikes via models. Front Cell Neurosci. 12:181. https://doi.org/10.3389/fncel.2018.00181
• Roy M, Sorokina O, McLean C, Tapia-González S, DeFelipe J, Armstrong JD, Grant SGN (2018) Regional diversity in the postsynaptic proteome of the mouse brain. Proteomes. https://doi.org/10.3390/proteomes6030031
• Santuy A, Turégano-López M1, Rodríguez JR, Alonso-Nanclares L, DeFelipe J, Merchán-Pérez A  (2018) A Quantitative study on the distribution of mitochondria in the neuropil of the juvenile rat somatosensory cortex. Cereb Cortex 28:3673–3684. http://dx.doi.org/10.1093/cercor/bhy159
• Zhu F, Cizeron M, Qiu Z, Benavides-Piccione R, Kopanitsa MV, Skene NG, Koniaris B, DeFelipe J, Fransén E, Komiyama NH3, Grant SGN (2018) Architecture of the mouse brain synaptome. Neuron 99:781-799. https://doi.org/10.1016/j.neuron.2018.07.007
• León-Espinosa G, Antón-Fernández A, Tapia-González S, DeFelipe J, Muñoz A (2018) Modifications of the axon initial segment during the hibernation of the Syrian hamster. Brain Struct Funct. 223:4307-4321. https://doi.org/10.1007/s00429-018-1753-7
• Rockland KS and DeFelipe J (2018) Editorial: Why Have Cortical Layers? What Is the function of layering? Do neurons in cortex integrate information across different layers? Front Neuroanat. 12:78. https://doi.org/10.3389/fnana.2018.00078
• Merino-Serrais P, Loera-Valencia R, Rodriguez-Rodriguez P, Parrado-Fernandez C, Ismail MA, Maioli S, Matute E, Jimenez-Mateos EM, Björkhem I, DeFelipe J, Cedazo-Minguez A (2018) 27- Hydroxycholesterol induces aberrant morphology and synaptic dysfunction in hippocampal neurons. Cereb Cortex 29:429-446. https://doi.org/10.1093/cercor/bhy274
• Mihaljević B,Larrañaga, P, Benavides-Piccione R, Hill S, DeFelipe J, & Bielza C (2018) Towards a supervised classification of neocortical interneuron morphologies. BMC bioinformatics, 19(1), 511. https://doi.org/10.1186/s12859-018-2470-1
• Aliaga Maraver JJ, Mata S, Benavides-Piccione R, DeFelipe, J, Pastor L (2018) A Method for the symbolic representation of neurons. Front Neuroanat. 12:106. https://doi.org/10.3389/fnana.2018.00106
• Kwon T, Merchán-Pérez A, Rial Verde EM, Rodríguez JR, DeFelipe J, Yuste R (2019) Ultrastructural, molecular and functional mapping of GABAergic synapses on dendritic spines and shafts of neocortical pyramidal neurons. Cereb Cortex 29:2771–2781. https://doi.org/10.1093/cercor/bhy143
• Gonzalez-Riano C, Leon-Espinosa G, Regalado-Reyes M, García A, DeFelipe J, Barbas C (2019) A Metabolomic study of hibernating Syrian hamster brain: in search of neuroprotective agents J Proteome Res. 18:1175–1190 https://doi.org/10.1021/acs.jproteome.8b00816
• León-Espinosa G, DeFelipe J, Muñoz A (2019) The Golgi apparatus of neocortical glial cells during hibernation in the Syrian hamster. Front Neuroant.13: 92. https://doi.org/10.3389/fnana.2019.00092
• Leguey I, Benavides-Piccione R, Rojo C, Larrañaga P, Bielza C, DeFelipe J (2019) Patterns of dendritic basal field orientation of pyramidal neurons in the rat somatosensory cortex. eNeuro, 5(6), ENEURO.0142-18.2018. https://doi.org/10.1523/eneuro.0142-18.2018
• Regalado-Reyes M, Furcila D, Hernández F, Ávila J, DeFelipe J, León-Espinosa G (2019) Phospho-tau changes in the human CA1 during Alzheimer’s disease progression. J Alzheimers Dis, 69(1): 277–288. https://doi.org/10.3233/JAD-181263
• Domínguez-Álvaro M, Montero-Crespo M, Blázquez-Llorca L, DeFelipe J, Alonso-Nanclares L (2019) 3D electron microscopy study of synaptic organization of the normal human transentorhinal cortex and its possible alterations in Alzheimer’s disease. eNeuro. pii: ENEURO.0140-19.2019 https://doi.org/10.1523/eneuro.0140-19.2019
• Furcila D, Domínguez-Álvaro M, DeFelipe J, Alonso-Nanclares L (2019) Subregional density of neurons, neurofibrillary tangles and amyloid plaques in the hippocampus of patients with Alzheimer’s disease. Front Neuroanat. 13:99. https://doi.org/10.3389/fnana.2019.00099
• Ortuño T, López-Madrona VJ, Makarova J, Tapia-González S, Muñoz A, DeFelipe J, Herreras O. 019. Slow-wave activity in the S1hl cortex is contributed by different layer-specific field potential sources during development. J Neurosci. 39:8900–8915. https://doi.org/10.1523/jneurosci.1212-19.2019
• Mihaljević B, Benavides-Piccione R, Bielza C, Larrañaga P, DeFelipe J (2019) Classification of GABAergic interneurons by leading neuroscientists. Sci Data. 26(1):221. https://doi.org/10.1038/s41597-019-0246-8
• Tapia-González S, Insausti R, DeFelipe J (2019) Differential expression of secretagogin immunostaining in the hippocampal formation and the entorhinal and perirhinal cortices of humans, rats, and mice. J Comp Neurol 528:523-541. https://doi.org/10.1002/cne.24773
• Benavides-Piccione R, Regalado-Reyes M, Fernaud-Espinosa I, Kastanauskaite A, TapiaGonzález S, León-Espinosa G, Rojo C, Insausti R, Segev I, DeFelipe J (2020) Differential structure of hippocampal CA1 pyramidal neurons in the human and mouse. Cereb Cortex 30:730- 752. https://doi.org/10.1093/cercor/bhz122
• Turegano-Lopez M, Santuy A, DeFelipe J, Merchan-Perez A (2020) Size, shape, and distribution of multivesicular bodies in the juvenile rat somatosensory cortex: A 3D electron microscopy study. Cereb Cortex. 30:1887-1901. http://dx.doi.org/10.1093/cercor/bhz211
• Merino-Serrais P, Tapia-González S, DeFelipe J (2020) Calbindin immunostaining in the CA1 hippocampal pyramidal cell layer of the human and mouse: A comparative study. J Chem Neuroanat. 104:101745. https://doi.org/10.1016/j.jchemneu.2020.101745
• Kikuchi T, Gonzalez-Soriano J, Kastanauskaite A, Benavides-Piccione R, Merchan-Perez A, DeFelipe J, Blazquez-Llorca L (2020) Volume electron microscopy study of the relationship between synapses and astrocytes in the developing rat somatosensory cortex. Cereb Cortex. 30:3800–3819. https://doi.org/10.1093/cercor/bhz343
• Montero-Crespo M, Domínguez-Álvaro M, Rondón-Carrillo P, Alonso-Nanclares L, DeFelipe J, Blázquez-Llorca L (2020) Three-dimensional synaptic organization of the human hippocampal CA1 field. eLife 2020;9:e57013. https://doi.org/10.7554/eLife.57013
• Rodriguez-Moreno J, Porrero C, Rollenhagen A, Rubio-Teves M, et al (2020) Area-specific synapse structure in branched posterior nucleus axons reveals a new level of complexity in thalamocortical networks. J Neurosci. 40:2663 2679. https://doi.org/10.1523/JNEUROSCI.2886-19.2020
• Yuste R, Hawrylycz M, Aalling N, Aguilar-Valles A, Arendt D, et al  (2020) A community-based transcriptomics classification and nomenclature of neocortical cell types. Nat Neurosci. 23:1456- 1468. https://dx.doi.org/10.1038%2Fs41593-020-0685-8
• Mihaljević B, Larrañaga P, Benavides-Piccione R, DeFelipe J, Bielza C (2020) Comparing basal dendrite branches in human and mouse hippocampal CA1 pyramidal neurons with Bayesian networks. Sci Rep. 10(1):18592. https://doi.org/10.1038/s41598-020-73617-9
• Santuy A, Tomás-Roca L, Rodríguez JR, González-Soriano J, Zhu F, Qiu Z, Grant SGN, DeFelipe J, Merchan-Perez A (2020) Estimation of the number of synapses in the hippocampus and brainwide by volume electron microscopy and genetic labeling. Sci Rep. 10(1):14014. https://doi.org/10.1038/s41598-020-70859-5
• Velasco I, Toharia P, Benavides-Piccione R, Fernaud-Espinosa I, Brito JP, Mata S, DeFelipe J, Pastor L, Bayona S (2020) Neuronize v2: bridging the gap between existing proprietary tools to optimize neuroscientific workflows. Front Neuroanat. 14:585793. https://doi.org/10.3389/fnana.2020.585793
• Regalado-Reyes M, Benavides-Piccione R, Fernaud-Espinosa I, DeFelipe J, León-Espinosa G (2020) Effect of phosphorylated tau on cortical pyramidal neuron morphology during hibernation. Cereb Cortex Communications. 1:1-25. https://doi.org/10.1093/texcom/tgaa018
• Domínguez-Álvaro M, Montero-Crespo L Blazquez-Llorca, DeFelipe J, Alonso-Nanclares L (2021) 3D Ultrastructural study of synapses in the human entorhinal cortex. Cereb Cortex. 31:410–425. https://doi.org/10.1093/cercor/bhaa233
• DeFelipe J, De Carlos JA, Metha AR (2021) A museum for Cajal’s Legacy. The Lancet Neurology.20(1):25. https://doi.org/10.1016/S1474-4422(20)30444-0
• Montero-Crespo M, Domínguez-Álvaro M, Alonso-Nanclares L, DeFelipe J, Blazquez-Llorca L (2021) Three-dimensional analysis of synaptic organization in the hippocampal CA1 region in Alzheimer’s disease. Brain. 144(2):553-573. https://doi.org/10.1093/brain/awaa406
• Loera-Valencia R, Vazquez-Juarez E, Muñoz A, Gerenu G, Gómez-Galán M, Lindskog M, DeFelipe J, Cedazo-Minguez A, Merino-Serrais P (2021) High levels of 27-hydroxycholesterol results in synaptic plasticity alterations in the hippocampus. Sci Rep. 11(1):3736. https://doi.org/10.1038/s41598-021-83008-3
• Blazquez-Llorca L, Miguéns M, Montero-Crespo M, Selvas A, Gonzalez-Soriano J, Ambrosio E, DeFelipe J (2021) 3D synaptic organization of the rat CA1 and alterations induced by cocaine self-administration. Cereb Cortex. 31(4):1927-1952. https://doi.org/10.1093/cercor/bhaa331
• Gonzalez-Riano C, Tapia-González S, Perea G, González-Arias C, DeFelipe J, Barbas C (2021)Metabolic changes in brain slices over time: a multiplatform metabolomics approach. Mol Neurobiol. 58:3224–3237. https://doi.org/10.1007/s12035-020-02264-y32
• Benavides-Piccione R, Rojo C, Kastanauskaite A, DeFelipe J (2021) Variation in pyramidal cellmorphology across the human anterior temporal lobe. Cereb cortex 31(8):3592–3609. https://doi.org/10.1093/cercor/bhab034
• Cano-Astorga N, DeFelipe J, Alonso-Nanclares L(2021) Three-dimensional synaptic organization of layer III of the human temporal neocortex. Cereb Cortex bhab120. https://doi.org/10.1093/cercor/bhab120
• Maestú F, de Haan W, Busche MA, DeFelipe J. 2021. Neuronal excitation/inhibition imbalance: core element of a translational perspective on Alzheimer pathophysiology. Ageing Research Reviews. 69:101372. https://doi.org/10.1016/j.arr.2021.101372
• Domínguez-Álvaro M, Montero-Crespo M, Blazquez-Llorca L, Plaza-Alonso S, Cano-Astorga N, DeFelipe J, Alonso-Nanclares L (2021) 3D analysis of the synaptic organization in the entorhinal cortex in Alzheimer’s disease. eNeuro.0504-20.2021. https://doi.org/10.1523/ENEURO.0504-20
• LaTorre A, Alonso-Nanclares L, Peña JM, DeFelipe J (2021) 3D segmentation of neuronal nuclei and cell-type identification using multi-channel information. Expert Syst Appl. 183:115443. https://doi.org/10.1016/j.eswa.2021.115443
• Luján R, Merchán-Pérez A, Soriano J, Martín-Belmonte A, Aguado C, Alfaro-Ruiz R, MorenoMartínez AE and DeFelipe J (2021) Neuron class and target variability in the three-dimensional localization of sk2 channels in hippocampal neurons as detected by immunogold FIB-SEM. Front. Neuroanat. 15:781314. doi: 10.3389/fnana.2021.781314
• Vidaurre-Gallart I, Fernaud-Espinosa I, Cosmin-Toader N, Talavera-Martínez L, Martin-Abadal M, Benavides-Piccione R, Gonzalez-Cid Y, Pastor L, DeFelipe J and García-Lorenzo M (2022) A deep learning-based workflow for dendritic spine segmentation. Front. Neuroanat. 16:817903. doi: 10.3389/fnana.2022.817903
• Amunts K, DeFelipe J, Pennartz C, Destexhe A, Migliore M, Ryvlin P, Furber S, Knoll A, Bitsch L, Bjaalie JG, Ioannidis Y, Lippert T, Sanchez-Vives MV, Goebel R, Jirsa V (2022). Linking brain structure, activity and cognitive function through computation. eNeuro. ENEURO.0316- 21.2022. doi: 10.1523/ENEURO.0316-21.2022
• Merino-Serrais P, Plaza-Alonso S, Hellal F, Valero-Freitag S, Kastanauskaite A, Muñoz A, Plesnila N, DeFelipe J (2022). Microanatomical study of pyramidal neurons in the contralesional somatosensory cortex after experimental ischemic stroke. Cereb Cortex bhac121. doi: 10.1093/cercor/bhac121.
• Turegano-Lopez M, Santuy A, Kastanauskaite A, Rodriguez JR, DeFelipe J, Merchan-Perez A (2022). Single-neuron labeling in fixed tissue and targeted volume electron microscopy. Front Neuroanat. 16:852057. doi: 10.3389/fnana.2022.852057.
• Antón-Fernández A, León-Espinosa,G, DeFelipe J, Muñoz A (2022). Pyramidal cell axon initial segment in Alzheimer´s disease. Sci Rep 12, 8722. https://doi.org/10.1038/s41598-022-12700-9
• Chindemi G, Abdellah M, Amsalem O, Benavides-Piccione R, Delattre V, Doron M, Ecker A, King J, Kumbhar P, Monney C, Perin R, Rössert C, Van Geit W, DeFelipe J, Graupner M, Segev I, Markram H, Muller E. (2022). A calcium-based plasticity model predicts long-term potentiation and depression in the neocortex. Nat Commun 13, 3038. https://doi.org/10.1038/s41467-022-30214-w
• Hunt S, Leibner Y, Mertens EJ, Barros-Zulaica N, Kanari L, Heistek TS, Karnani MM, Aardse R,Wilbers R, Heyer DB, Goriounova NA, Verhoog MB, Testa-Silva G, Obermayer J, Versluis T, Benavides-Piccione R, de Witt-Hamer P, Idema S, Noske DP, Baayen JC, Lein ES, DeFelipe J, Markram H, Mansvelder HD, Schürmann F, Segev I, de Kock CPJ (2022). Strong and reliable 33 synaptic communication between pyramidal neurons in adult human cerebral cortex. Cereb Cortex. bhac246. https://doi: 10.1093/cercor/bhac246
• DeFelipe J (2022) Manifesto of a neuroanatomist. Front. Neuroanat. 16:931547. https://www.frontiersin.org/articles/10.3389/fnana.2022.931547/full
• Bulovaite E, Qiu Z, Kratschke M, Zgraj A, Fricker DG, Tuck EJ, Gokhale R, Koniaris B, Jami SA, Merino-Serrais P, Husi E, Mendive-Tapia L, Vendrell M, O’Dell TJ, DeFelipe J, Komiyama NH, Holtmaat A, Fransén E, Grant SGN. A brain atlas of synapse protein lifetime across the mouse lifespan. Neuron. 2022 Sep 28:S0896-6273(22)00814-5. doi: 10.1016/j.neuron.2022.09.009.
• Ostos, S, Aparicio, G, Fernaud-Espinosa, I, DeFelipe, J and Muñoz A (2022) Quantitative analysis of the GABAergic innervation of the soma and axon initial segment of pyramidal cells in the human and mouse neocortex. Cereb Cortex. bhac314. doi: 10.1093/cercor/bhac314
• Alonso-Nanclares, L., Rodríguez, J. R., Merchan-Perez, A., González-Soriano, J., Plaza-Alonso, S., Cano-Astorga, N., et al. Cortical synapses of the world’s smallest mammal: An FIB/SEM study in the Etruscan shrew. J Comp Neurol. doi: 10.1002/cne.25432
• DeFelipe J, DeFelipe-Oroquieta J, Furcila D, Muñoz-Alegre M, Maestú F, Sola RG,  BlázquezLlorca L, Armañanzas R, Kastanaskaute A, Alonso-Nanclares L, Rockland KS and Arellano JI (2022) Neuroanatomical and psychological considerations in temporal lobe epilepsy. Front. Neuroanat. 16:995286. doi: 10.3389/fnana.2022.995286

Contact

Others