Alfonso Araque, Ph.D.

Professor, Department of Neuroscience

E-MAIL: [email protected]

Research Interests:

Research of my group focuses on the mechanisms and physiological consequences of the astrocyte-neuron signaling, aiming to understand its role in physiological and pathological aspects of synaptic physiology and brain function. Astrocytes, classically considered as supportive cells for neurons without a direct role in brain information processing, are emerging as relevant elements in brain physiology through their ability to regulate neuronal and synaptic activity. We are studying how astrocytes respond to neuronal activity, how they control neuronal activity and synaptic transmission and plasticity, and how they are involved in neural network function.

My previous work provided the first demonstration of regulation of synaptic transmission by astrocytes and the definition of the Tripartite Synapse concept, which represents a novel view of synaptic physiology. According to this concept, astrocytes are integral functional elements of synapses by exchanging information signals with neurons. My recent contributions include: the demonstration that astrocytes display integrative properties for synaptic information processing, the demonstration of astrocyte regulation of synaptic transmission at single synapses, the first description of astrocyte involvement in endocannabinoid signaling and its consequences on synaptic transmission; the first design of artificial AstroNeuronal networks -a novel concept in artificial intelligence-, and the demonstration that artificial astrocytes improve network performance; the demonstration of astrocyte-mediated synaptic plasticity in vivo; and the demonstration of astrocyte-neuron signaling in human brain tissue.

We are currently investigating the cellular mechanisms and physio-pathological consequences of astrocyte-neuron interactions in different brain areas to test the working hypothesis that brain function results from the operation of AstroNeuronal networks established by the coordinated activity of astrocytes and neurons. We are also interested in deciphering the contribution of the altered function of Tripartite Synapses and AstroNeuronal networks to brain diseases.

Selected Publications:

(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)

  • Nanclares C, Noriega-Prieto JA, Labrada-Moncada FE, Cvetanovic M, Araque A, Kofuji P. Altered calcium signaling in Bergmann glia contributes to spinocerebellar ataxia type-1 in a mouse model of SCA1. Neurobiol Dis. 2023 Oct 4:106318. 
  • Goenaga J, Araque A, Kofuji P, Herrera Moro Chao D. Calcium signaling in astrocytes and gliotransmitter release. Front Synaptic Neurosci. 2023 Mar 2;15:1138577.
  • Brown JL, Boyle GS, hard D, Brown TG, LaCroix M, Kim M, Sherman MA, Boes S, Seung M, Cole T, Lee MK, Araque A, Lesne SE. SNCA genetic lowering reveals differential cognitive function of alpha-synuclein dependent on sex. Acta Neuropathol Commun. in press, 2023.
  • Noriega-Prieto JA, Kofuji P, Araque A. Endocannabinoid signaling in synaptic function. Glia. 2023 Jan;71(1):36-43.
  • Marsicano G, Araque A. Of glue and pot: Endocannabinoid signaling in glial cells. Glia. 2023 Jan;71(1):3-4.
  • Yu D, Zarate N, White A, Coates D, Tsai W, Nanclares C, Cuccu F, Yue JS, Brown TG, Mansky RH, Jiang K, Kim H, Nichols-Meade T, Larson SN, Gundry K, Zhang Y, Tomas-Zapico C, Lucas JJ, Benneyworth M, Öz G, Cvetanovic M, Araque A, Gomez-Pastor R. CK2 alpha prime and alpha-synuclein pathogenic functional interaction mediates synaptic dysregulation in huntington's disease. Acta Neuropathol Commun. 2022 Jun 3;10(1):83. Erratum in: Acta Neuropathol Commun. 2022 Jun 22;10(1):89.
  • Lines J, Baraibar AM, Fang C, Martin ED, Aguilar J, Lee MK, Araque A, Kofuji P. Astrocyte-neuronal network interplay is disrupted in Alzheimer's disease mice. Glia. 2022;70(2):368-378.
  • Nanclares C, Baraibar AM, Araque A, Kofuji P. Dysregulation of astrocyte-neuronal communication in Alzheimer's disease. Int J Mol Sci. 2021 Jul 23;22(15):7887.
  • Durkee C, Kofuji P, Navarrete M, Araque A. Astrocyte and neuron cooperation in long-term depression. Trends Neurosci. 2021 Oct;44(10):837-848.
  • Corkrum M, Araque A. Astrocyte-neuron signaling in the mesolimbic dopamine system: the hidden stars of dopamine signaling. Neuropsychopharmacology. 2021 Oct;46(11):1864-1872.
  • Kofuji P, Araque A. Astrocytes control the critical period of circuit wiring. Science. 2021 Jul 2;373(6550):29-30.
  • Noriega-Prieto JA, Araque A. Sensing and regulating synaptic activity by astrocytes at tripartite synapse. J Neurosci. 2021 Jun 2;41(22):4768-4781.
  • Fernández de Sevilla D, Nuñez A, Araque A, Buño W. Metabotropic regulation of synaptic plasticity.  Neuroscience. 2021 Feb 21;456:1-3.
  • Kofuji P, Araque A. Astrocytes and Behavior. Annu Rev Neurosci. 2021;4: in press. Jan 6;. doi: 10.1146/annurev-neuro-101920-112225.
  • Lines J, Martin ED, Kofuji P, Aguilar J, Araque A. Astrocytes modulate sensory-evoked neuronal network activity. Nat Commun. 2020;11(1):3689.
  • Corkrum M, Covelo A, Lines J, Bellocchio L, Pisansky M, Loke K, Quintana R, Rothwell PE, Lujan R, Marsicano G, Martin ED, Thomas MJ, Kofuji P, Araque A. Dopamine-evoked synaptic regulation in the nucleus accumbens requires astrocyte activity. Neuron. 2020 Mar 18;105(6):1036-1047.
  • Cavaccini A, Durkee C, Kofuji P, Tonini R, Araque A. Astrocyte signaling gates long-term depression at corticostriatal synapses of the direct pathway. J Neurosci. 2020 Jun 15. pii: JN-RM-2369-19.
  • Kofuji P, Araque A. G-protein-coupled receptors in astrocyte-neuron communication. Neuroscience. 2020 Mar 26. pii: S0306-4522(20)30177-9.
  • Corkrum M, Covelo A, Lines J, Bellocchio L, Pisansky M, Loke K, Quintana R, Rothwell PE, Lujan R, Marsicano G, Martin ED. Thomas MJ, Kofuji P, Araque A. Dopamine-evoked synaptic regulation in the nucleus accumbens requires astrocyte activity. Neuron. 2020;105(6):1036-1047.
  • Fullana MN, Covelo A, Bortolozzi A, Araque A, Artigas F. In vivo knockdown of astroglial glutamate transporters GLT-1 and GLAST increases excitatory neurotransmission in mouse infralimbic cortex: Relevance for depressive-like phenotypes. Eur Neuropsychopharmacol. 2019;29(11):1288-1294.
  • Corkrum M, Rothwell PE, Thomas MJ, Kofuji P, Araque A. Opioid-mediated astrocyte-neuron signaling in the nucleus accumbens.Cells. 2019 Jun 14;8(6). pii: E586.
  • Liu J, McDaid L, Araque A, Wade J, Harkin J, Karim S, Henshall DC, Connolly NMC, Johnson AP, Tyrrell AM, Timmis J, Millard AG, Hilder J, Halliday DM. GABA regulation of burst firing in hippocampal astrocyte neural circuit: A biophysical model. Front Cell Neurosci. 2019 Jul 23;13:335.
  • Kofuji P, Araque A. Swelling gliotransmission by SWELL1 channels. Neuron. 2019;102(4):711-713.
  • Singh B, Covelo A, Martell-Martínez H, Nanclares C, Sherman MA, Okematti E, Meints J, Teravskis PJ, Gallardo C, Savonenko AV, Benneyworth MA, Lesné SE, Liao D, Araque A, Lee MK. Tau is required for progressive synaptic and memory deficits in a transgenic mouse model of α-synucleinopathy. Acta Neuropathol. 2019;138(4):551-574.
  • Durkee CA, Covelo A, Lines J, Kofuji P, Aguilar J, Araque A. Gi/o protein-coupled receptors inhibit neurons but activate astrocytes and stimulate gliotransmission. Glia. 2019;67(6):1076-1093.
  • García-Cáceres C, Balland E, Prevot V, Luquet S, Woods SC, Koch M, Horvath TL, Yi CX, Chowen JA, Verkhratsky A, Araque A, Bechmann I, Tschöp MH. Role of astrocytes, microglia, and tanycytes in brain control of systemic metabolism. Nat Neurosci. 2018 Dec 10. doi: 10.1038/s41593-018-0286-y.
  • Durkee CA, Araque A. Diversity and specificity of astrocyte-neuron communication. Neuroscience. 2019 Jan 1;396:73-78.
  • Teravskis PJ, Covelo A, Miller EC, Singh B, Martell-Martínez HA, Benneyworth MA, Gallardo C, Oxnard BR, Araque A, Lee MK, Liao D. A53T mutant alpha-synuclein induces tau dependent postsynaptic impairment independent of neurodegenerative changes. J Neurosci. 2018;38:9754-9767.
  • Covelo A, Araque A. Stimulating astrocytes to remember. Cell. 2018 Jun 28;174(1):12-13.
  • Covelo A, Araque A. Neuronal activity determines distinct gliotransmitter release from a single astrocyte. Elife. 2018 Jan 30;7. pii: e32237.
  • Lines J, Covelo A, Gómez R, Liu L, Araque A. Synapse-specific regulation revealed at single synapses Is concealed when recording multiple synapses. Front Cell Neurosci. 2017;11:367.
  • Martin-Fernandez M, Jamison S, Robin LM, Zhao Z, Martin ED, Aguilar J, Benneyworth MA, Marsicano G, Araque A. Synapse-specific astrocyte gating of amygdala-related behavior. Nat Neurosci. 2017;20(11):1540-1548.
  • Araque A, Castillo PE, Manzoni OJ, Tonini R. Synaptic functions of endocannabinoid signaling in health and disease. Neuropharmacology. 2017;124:13-24.
  • Gómez-Gonzalo M, Martin-Fernandez M, Martínez-Murillo R, Mederos S, Hernández-Vivanco A, Jamison S, Fernandez AP, Serrano J, Calero P, Futch HS, Corpas R, Sanfeliu C, Perea G, Araque A. Neuron-astrocyte signaling is preserved in the aging brain. Glia. 2017;65(4):569-580.
  • Fernandez AM, Hernandez-Garzón E, Perez-Domper P, Perez-Alvarez A, Mederos S, Matsui T, Santi A, Trueba-Saiz A, García-Guerra L, Pose-Utrilla J, Fielitz J, Olson EN, Fernandez de la Rosa R, Garcia Garcia L, Pozo MA, Iglesias T, Araque A, Soya H, Perea G, Martin ED, Torres Aleman I. Insulin regulates astrocytic glucose handling through vooperation with IGF-I. Diabetes. 2017;66(1):64-74.
  • Perea G, Gómez R, Mederos S, Covelo A, Ballesteros JJ, Schlosser L, Hernández-Vivanco A, Martín-Fernández M, Quintana R, Rayan A, Díez A, Fuenzalida M, Agarwal A, Bergles DE, Bettler B, Manahan-Vaughan D, Martín ED, Kirchhoff F, Araque A. Activity-dependent switch of GABAergic inhibition into glutamatergic excitation in astrocyte-neuron networks. Elife. 2016 Dec 24;5. pii: e20362.
  • Hernandez-Garzón E, Fernandez AM, Perez-Alvarez A, Genis L, Bascuñana P, Fernandez de la Rosa R, Delgado M, Angel Pozo M, Moreno E, McCormick PJ, Santi A, Trueba-Saiz A, Garcia-Caceres C, Tschöp MH, Araque A, Martin ED, Torres Aleman I. The insulin-like growth factor I receptor regulates glucose transport by astrocytes. Glia. 2016;64(11):1962-1971.
  • Covelo A, Araque A. Lateral regulation of synaptic transmission by astrocytes. Neuroscience. 2016;323:62-66.
  • Gómez-Gonzalo M, Navarrete M, Perea G, Covelo A, Martín-Fernández M, Shigemoto R, Luján R, Araque A. Endocannabinoids induce lateral long-term potentiation of transmitter release by stimulation of gliotransmission. Cereb Cortex. 2015;25(10):3699-36712.
  • Martin R, Bajo-Grañeras R, Moratalla R, Perea G, Araque A. Circuit-specific signaling in astrocyte-neuron networks in basal ganglia pathways. Science 2015;349:730-734.
  • Oliveira JF, Sardinha VM, Guerra-Gomes S, Araque A, Sousa N. Do stars govern our actions? Astrocyte involvement in rodent behavior. Trends Neurosci. 2015;38:535-549.
  • Jego P, Pacheco-Torres J, Araque A, Canals S. Functional MRI in mice lacking IP3-dependent calcium signaling in astrocytes. J Cereb Blood Flow Metab. 2014;34(10):1599-603.
  • Navarrete M, Díez A, Araque A. Astrocytes in endocannabinoid signalling. Philos Trans R Soc Lond B Biol Sci. 2014;369(1654):20130599.
  • Perez-Alvarez A, Navarrete M, Covelo A, Martin ED, Araque A. Structural and functional plasticity of astrocyte processes and dendritic spine interactions. J Neurosci. 2014;34(38):12738-12744.
  • Perea G, Sur M, Araque A. Neuron-glia networks: integral gear of brain function. Front Cell Neurosci.2014; 8:378.
  • Araque A, Carmignoto G, Haydon PG, Oliet SH, Robitaille R, Volterra A. Gliotransmitters travel in time and space. Neuron. 2014;81(4):728-739.
  • Araque A, Camignoto G, Haydon PG, Oliet SH, Robitaille R, Volterra A. Gliotransmitters travel in time and space. Neuron 2014;81:728-739.   

Current Graduate Students:

Julianna Goenaga (Neuroscience, University of Minnesota). 
Jacob Noeker (Neuroscience, University of Minnesota).

Former Graduate Students:

Austin Ferro (Ph.D. 2020, Neuroscience, University of Minnesota) 
Justin Lines (Ph.D. 2020, Neuroscience, University of Minnesota). 
Michelle Corkrum (Ph.D. 2019, Neuroscience, University of Minnesota). 
Caitlin Durkee (Ph.D. 2019, Neuroscience, University of Minnesota).


Picture of Alfonso Araque