Group leader: Glenn Dallérac

Astrocytes and Cognition

In brief

Information processing enabling brain sensory and cognitive performances is typically thought to fully rely on neurons. Yet, the other major cell type in the brain, the astrocytes, has now been shown to play a key role in brain activity and pathology. Astroglial cells can indeed sense neuronal inputs through membrane ion channels, transporters and receptors. They can also respond by transduction pathways, involving for instance calcium signaling, and modulate in turn adjacent neuronal elements by various mechanisms, including uptake or release of neuroactive factors, contact-mediated signaling or plastic physical coverage of neurons. However, comprehensive molecular description of such regulations, their occurrence and impact during physiological or pathological conditions remains to be further described. Furthermore, little is known about the impact of such regulation on perception, behavior and cognition. Unraveling how astrocytes control the activity of neuronal circuits and brain functions is important, not only to advance our comprehension of cognitive functions, but also to provide a novel framework for identifying dysfunctions underlying neurological disorders as well as alternative therapeutic targets.

Our research tackles 2 main aspects of neuroglial interactions :

1- Neuroglial control of monoamines regulations
Recent data indicate that astrocytes regulate prefrontal cortex neuronal activity through the control of monoamines concentrations (Petrelli, Dallérac et al 2018). As this control implies astroglial expression of the vesicular transporter for monoamine VMAT2, our team investigates whether and how astrocytes can control the release of neuromodulators and thereby influence cognitive functions relying on prefrontal activity. Further, VMAT2 as well as the membrane dopamine transporter DAT were also found to be expressed in Bergmann glial cells, a specialized type of astroglia unique to the cerebellum. These features being atypical in astroglial cells, we investigate the role of these monoamine transporters in the modulation of cerebellar functions.

2- Role of astrocytes in developmental critical periods
In the immature brain a both neurons and glial cells develop in parallel during critical periods of postnatal development characterized by enhanced plasticity processes. Remarkably, pioneer data point to key role of astrocytes in the control of the opening and closing of these critical periods (Muller & Best 1989). However, how immature astrocytes operate remains unknown. Our team investigate the mechanisms through which astrocytes regulate sensitive periods of plasticity, key to the development of perception, behavior and cognition.

These research axes engage a multidisciplinary approach including ex vivo and in vivo electrophysiology and imaging, optogenetic tools, as well as behavioral analyses coupled to classical immunohistochemistry and biochemsistry techniques.

Selected Publications

  • Ribot J*, Breton R*, Calvo CF, Moulard J, Ezan P, Zapata J, Samama K, Moreau M, Bemelmans AP, Sabatet V, Dingli F, Loew D, Milleret C, Billuart P, Dallérac G£, Rouach N£. Astrocytes close the mouse critical period for visual plasticity. Science. 373(6550):77-81 *co-first authors. £co-last authors.
  • Dallérac G, Li X, Lecouflet P, Morisot N, Sacchi S, Asselot R, Pham TH, Potier B, Watson D, Schmidt S, Levasseur G, Fossat P, Besedin A, Rivet JM, Coyle J, Collo G, Pollegioni L, Kehr J, Galante M, Fone K, Gardier A, Freret T, Contarino A, Millan M, Mothet JP. Dopaminergic neuromodulation of prefrontal cortex activity requires the NMDA receptor co-agonist d-serine. 2021. Proceedings of the National Academy of Science of the United States of America. 118(23):e2023750118.
  • Cutando L, Puighermanal E, Castell L, Tarot P, Bertaso F, Bonnavion P, de Kerchove d’Exaerde A, Isingrini E, Galante M, Dallérac G, Pascoli V, Lüscher C, Giros B, Valjent E. Regulation of GluA1 Phosphorylation by D-amphetamine and Methylphenidate in the Cerebellum. Addiction Biology. 26(4):e12995
  • Dallérac G, Zapata J, Rouach N. Versatile control of synaptic circuits by astrocytes: where, when and how? 2018. Nature Reviews Neurosciences.19(12):729-743. 
  • Petrelli F*, Dallérac G*, Pucci L*, Calì C*, Zehnder T, Sultan S, Lecca S, Chicca A, Ivanov A, Asensio CS, Gundersen V, Toni N, Knott GW, Magara F, Gertsch J, Kirchhoff F, Déglon N, Giros B, Edwards RH, Mothet JP, Bezzi P. Dysfunction of homeostatic control of dopamine by astrocytes in the developing prefrontal cortex leads to cognitive impairments. Molecular Psychiatry 25(4):732-749. *co-first authors.

Team leader

Members

  • Ribot J*, Breton R*, Calvo CF, Moulard J, Ezan P, Zapata J, Samama K, Moreau M, Bemelmans AP, Sabatet V, Dingli F, Loew D, Milleret C, Billuart P, Dallérac G£, Rouach N£. Astrocytes close the mouse critical period for visual plasticity. Science. 373(6550):77-81 *co-first authors. £ co-last authors.
  • Dallérac G, Li X, Lecouflet P, Morisot N, Sacchi S, Asselot R, Pham TH, Potier B, Watson D, Schmidt S, Levasseur G, Fossat P, Besedin A, Rivet JM, Coyle J, Collo G, Pollegioni L, Kehr J, Galante M, Fone K, Gardier A, Freret T, Contarino A, Millan M, Mothet JP. Dopaminergic neuromodulation of prefrontal cortex activity requires the NMDA receptor co-agonist d-serine. 2021. Proceedings of the National Academy of Science of the United States of America. 118(23):e2023750118.
  • Cutando L, Puighermanal E, Castell L, Tarot P, Bertaso F, Bonnavion P, de Kerchove d’Exaerde A, Isingrini E, Galante M, Dallérac G, Pascoli V, Lüscher C, Giros B, Valjent E. Regulation of GluA1 Phosphorylation by D-amphetamine and Methylphenidate in the Cerebellum. Addiction Biology. 26(4):e12995
  • Dallérac G, Zapata J, Rouach N. Versatile control of synaptic circuits by astrocytes: where, when and how? 2018. Nature Reviews Neurosciences.19(12):729-743. 
  • Petrelli F*, Dallérac G*, Pucci L*, Calì C*, Zehnder T, Sultan S, Lecca S, Chicca A, Ivanov A, Asensio CS, Gundersen V, Toni N, Knott GW, Magara F, Gertsch J, Kirchhoff F, Déglon N, Giros B, Edwards RH, Mothet JP, Bezzi P. Dysfunction of homeostatic control of dopamine by astrocytes in the developing prefrontal cortex leads to cognitive impairments. Molecular Psychiatry 25(4):732-749. *co-first authors.