Experimental Neurophysiology

Principal investigators:

Dr. Juan de los Reyes Aguilar Lepe

Dra. Juliana M Rosa

The goal of our group is to understand how circuits of neurons and astroglia cells encoding sensory stimuli are remodelled after traumatic spinal cord and brain injuries to give rise to new patterns of sensorimotor behaviour.

Our lab is headed by: Dr. Juan Aguilar whom leads the system physiology research line, and Dr. Juliana M Rosawhom leads the neuronal circuits and astrocyte-neuron interaction research lines.

Research and Aims:

Our research is focused on understanding the physiology of brain structures forming the somatosensory and motor system (primary somatosensory and motor cortex, somatosensory thalamus – VPL and POm) in health and after traumatic spinal cord and brain injuries. Our goal is to understand the mechanisms by which brain structures undergo neuronal plasticity in order to find new strategies to improve functional sensorimotor recovery. In addition, we also study the supraspinalmechanism underlying the appearance of sensory pathologies usually associated with traumatic spinal cord injury such as neuropathic and phantom limb pain.

In 2019, we opened a new research line in the lab focused in the study of the neuron-glia circuit dynamics. The major goal of this line is to elucidate the mechanisms by which neurons and glial cells interact to remodel brain circuits and to promote repair following traumatic injuries. Our special interest is focused on the manipulation of astrocyte and microglia activity in order to have a spatial-temporal control of neuronal activity related to sensorimotor behaviour.

Main research lines: In our current and future work, we aim to:

1) Determine the role of cortical and thalamic astrocytes in the processing of sensory information in health and after traumatic CNS injuries.

2) Study the relationship between alterations in local neuronal circuits within somatosensory cortical and thalamic regions and the appearance of sensory pathologies associated to traumatic spinal cord and brain injury.

3) Explore and develop new strategies to manipulate the astrocyte-neuron interaction to promote neural circuits repair and functional recovery after CNS injuries.

Techniques:

Our work relies on in vivo electrophysiology (awake and anaesthetized), neuronal whole-cell patch clamp recordings using brain slices, in vivo viral gene delivery techniques, pharmacogenetics, state-of-the-art imaging approaches, behaviour and programming and bioinformatics (Matlab, Spike, IgorPro).

Selected publications

(*Access the full list of publications by clickingon the Researcher’s CV)

1. Rosa JM*, Farre-Alins V, Navarrete M, Palomino-Antolin A, Narros-Fernández P,Egea J* (2021). Microglia-to-astrocyte communication modulates synaptic and cerebrovascular functions following traumatic brain injury. British Journal of PharmacologyDOI: 10.1101/2020.03.01.972158*corresponding (D1, IF 7.8)

2. Lines J, Martin ED, Kofuji P, Aguilar J*, Araque A*. (2020). Astrocytes modulate sensory-evoked neuronal network activity. Nature Communications 11: 3689 doi.org/10.1038/s41467-020-17536-3*corresponding (D1, IF 12.12)

3. Parada E, Casas AI, Palomino-Antolin A, Gomez_Rangel V, Rubio-Navarro A, Farre-Alins V, Narros-Fernandez P, Guerrero-Hue M, Moreno JA, Rosa JM, Hernandez-Garcia B, Egea J. Early toll-like receptor 4 blockade reduces ROS and inflammation triggered by microglial pro-inflammatory phenotype in rodent and human brain ischaemia models. (2019) British Journal of Pharmacology,doi.org/10.1111/bph.14703(D1, IF 7.8)

4. Fernández-López E, Alonso-Calviño E, Humanes-Varela D, Foffani G, Aguilar J*. (2019). Slow-wave activity homeostasis in the somatosensory cortex after spinal cord injury.Experimental Neurology. 322:113035 doi.org/10.1016/j.expneurol.2019.113035

5. Martin-Fernandez M, Jamison S, Robin LM, Zhao Z, Martin ED, Aguilar J, Benneyworth MA, Marsicano G, Araque A. (2017). Synapse-specific astrocyte gating of amygdala-related behavior.Nature Neuroscience 20(11):1540-1548 doi.org/10.1038/nn.4649(D1, IF 14.98)

6. Humanes-Valera D, Foffani G, Alonso-Calviño E, Fenández-López E, Aguilar J*. (2017). “Dual cortical plasticity after spinal cord injury”.Cerebral Cortex 27(5):2926-2940doi.org/10.1093/cercor/bhw142 (Q1, IF 8.66)

7. Rosa JM, Morrie RD, Baertchs HC, Feller M. (2016) Contributions of Rod and Cone Pathways to Retinal Direction Selectivity Through Development, The Journal of Neuroscience 36(37): 9683-9695. doi.org/10.1523/JNEUROSCI.3824-15.2016(Q1, IF 5.67)

8. Alonso-Calviño E,Martínez-Camero I, Fernández-López F, Humanes-Valera D, Foffani G, Aguilar J*. (2016). “Increased responses in the somatosensory thalamus immediately after spinal cord injury”.Neurobiology of Disease 87:39-49.doi.org/10.1016/j.nbd.2015.12.003 (Q1, IF 5.078)

9. Rosa JM, Ruhle S, Ding H, Lagnado L. (2016) Crossover Inhibition Generates Sustained Visual Responses in the Inner Retina, Neuron 90(2):308-19.doi.org/10.1016/j.neuron.2016.03.015 (D1, IF 14.4)

10. Rosa JM, Bos R, Sack GS, Fortuny C, Agarwal A, Bergles DE, Flannery JG, Feller M. (2015) Neuron-glia interaction in developing retina mediated by neurotransmitter spillover, eLife 10.7554. doi.org/10.7554/eLife.09590.001(D1, IF 8.2)

Pre-prints Actuales (bioRxiv):

- Zaforas M1, Rosa JM1, Alonso-Calvino E, Fernandez-Lopez, Miguel-Quesada C, Oliviero A, Aguilar J*. (2021). Cortical layer-specific modulation of neuronal activity after sensory deprivation due to spinal cord injury.bioRxiv. 28/12/2020DOI: 10.1101/2020.12.28.4246121co-authors.

Personnel.

Together We are a TEAM

Juan de los Reyes Aguilar Lepe (Principal Investigator)

Juliana M Rosa (Principal Investigator)

Salvador Herrera (Postdoctoral Researcher)

Elena Alonso Calvino (Lab Manager)

María Elena Fernández López (Lab Manager)

Marta Zaforas Rodríguez (PhD student)

Claudia Miguel Quesada (PhD student)

Alba María González (Master student)

Other research lines and collaborations:

1) Study of the effect of distinct biomaterials on the neuronal excitability (collaboration withDra. María Serrano LópezTerradas, Instituto de Materiales de Madrid, CSIC).

2) Role of astrocytes as modulators of neuronal activity (Dr. Alfonso Araque, University of Minnessota, USA)

3) Astrocytes as a therapeutic target to modulate neural circuits (Dra. Marta Navarrete, InstitutoCajal, CSIC)

4) Search for new glial-derived biomarkers as a prognostic tool for TBI (Dr. Javier Egea, Hospital de La Princesa, Madrid).

5) Properties of cortical neurons after magnetic stimulation (Dr. Antonio Oliviero andDra. Vanesa Soto, HNP)

6) Effects of Galectin-4 on cortical and hippocampal neuronal excitability (Dr. José Abad, HNP).

7) Effects of magnetic field as a modulator of epilepsy in rodents (Dr.CastaRivadulla, Universidad de Santiago de Compostela)

Ongoing projects

1. Papel de la poblacionesneuronalesGABAergicas en la reorganización cortical después de unalesiónmedular. EntidadFinanciadora: Ministerio de Ciencia e Innovación, PID2019-105020GB-100. Fecha: 2020-2023. Total 227.610 €
Investigador Principal: Juan de los Reyes Aguilar Lepe

2. Neural circuits repair after CNS injuries. EntidadFinanciadora: ProgramaRamón y Cajal, Ministerio de Ciencia e Innovación, Spanish Government, RYC2019-026870-I.Fecha: 2021-2026. Total: 308.600 €
investigador Principal: Juliana M Rosa

3. Efectos de los camposmagnéticosestáticossobre el cerebro: estudio de los mecanismos. Fundacion Ramón Areces. Fecha: 2020-2022. Total: 45.520 €

4. Cortical Reorganization after Spinal Cord Injury: role for astrocytes and interneurons.EntidadFinanciadora: Marie-Sklodowska Curie Actions Individual Grant 794926-CRASCI-H2020-MSCA-IF-2017.Fecha: 2018-2021. Total 170.121 €
InvestigadorPrincipal: Juliana M Rosa

5. Los segmentosaxonales no mielinizadoscomoreguladores de la plasticidad axonal asociada a la memoria y el aprendizaje: Caracterización molecular y funcional en el hipocampo. EntidadFinanciadora: Junta de Comunidades de Castilla-La Mancha, SBPLY/17/180501/000250. Fechas: 2018-2021. Total: 138.259 €
Co-investigador principal: Juan de los Reyes Aguilar Lepe

Previous projects

- Synaptic plasticity and remodelling in the somatosensory cortex after traumatic injuries.EntidadFinanciadora: RochePharma SFC2017, Fecha 2017-2019, Total: 60.000 €
Investigador Principal: Juliana M Rosa

- Fast and slow endocytosis at synapses.Marie-Sklodowska Curie Actions Individual Grant IEF (FSES-IEF-2010-272723), Fechas: 2011-2013, Total: 209.092 €
Investigador Principal: Juliana M Rosa

- Function of Neural Activity in Developing Retina. National Institute of Health, National Eye Institute. (University of California, Berkeley), Fecha: 2014-2015, Total: 715.075 $
InvestigadorAsociado: Juliana M Rosa

- Heterogeneidadespacial y temporal de la plasticidad neuronal provocadaporunalesiónmedular en la cortezasomatosensorial.Fechas: 2017-2019. Ref. BFU2016-80665-P. Ministerio de Economía y Competitividad.Gobierno de España. Total: 169.400 €
Investigador Principal: Juan de los Reyes Aguilar Lepe

- Efectosfisiológicosinmediatosproducidosporunalesiónmedular en el tálamosomatosensorial: Importancia de alteraciones del ritmo y sincronía. Fechas: 2013-2015. Ref. SAF2012-40109. Ministerio de Economía y Competitividad.Gobierno de España. Total:
Investigador Principal: Juan de los Reyes Aguilar Lepe

Patents

Title: Método para determinar la evolución de daño cerebral agudo y composición farmacéutica para su tratamiento
Inventores: Víctor Farré-Alins, Alejandra Palomino-Antolín, Paloma Narros-Fernández, Juliana M Rosa, Alfonso Lagares, Javier Egea
Nº de solicitud: P202031194
País de prioridad: España
Fecha de prioridad: 30/11/2020
Entidad titular: Fundaciónpara la Investigación Biomédica del Hospital Universitario La Princesa

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Experimental Neurophysiology