title: A New Computational Model for Neuro-Glio-Vascular Coupling: Astrocyte Activation Can Explain Cerebral Blood Flow Nonlinear Response to Interictal Events.
abstract: Developing a clear understanding of the relationship between cerebral blood flow (CBF) response and neuronal activity is of significant importance because CBF increase is essential to the health of neurons, for instance through oxygen supply. This relationship can be investigated by analyzing multimodal (fMRI, PET, laser Doppler…) recordings. However, the important number of intermediate (non-observable) variables involved in the underlying neurovascular coupling makes the discovery of mechanisms all the more difficult from the sole multimodal data. We present a new computational model developed at the population scale (voxel) with physiologically relevant but simple equations to facilitate the interpretation of regional multimodal recordings. This model links neuronal activity to regional CBF dynamics through neuro-glio-vascular coupling. This coupling involves a population of glial cells called astrocytes via their role in neurotransmitter (glutamate and GABA) recycling and their impact on neighboring vessels. In epilepsy, neuronal networks generate epileptiform discharges, leading to variations in astrocytic and CBF dynamics. In this study, we took advantage of these large variations in neuronal activity magnitude to test the capacity of our model to reproduce experimental data. We compared simulations from our model with isolated epileptiform events, which were obtained in vivo by simultaneous local field potential and laser Doppler recordings in rats after local bicuculline injection. We showed a predominant neuronal contribution for low level discharges and a significant astrocytic contribution for higher level discharges. Besides, neuronal contribution to CBF was linear while astrocytic contribution was nonlinear. Results thus indicate that the relationship between neuronal activity and CBF magnitudes can be nonlinear for isolated events and that this nonlinearity is due to astrocytic activity, highlighting the importance of astrocytes in the interpretation of regional recordings.
authors: Université de Rennes 1, INSERM U1099, Laboratoire Traitement du Signal et de l'Image, Rennes, France.
authors: Solenna
authors: S
authors: Blanchard
authors: Aix Marseille Université, INSERM UMRS 1106, Institut de Neurosciences des Systèmes, Marseille, France.
authors: Sandrine
authors: S
authors: Saillet
authors: Aix Marseille Université, INSERM UMRS 1106, Institut de Neurosciences des Systèmes, Marseille, France.
authors: Anton
authors: A
authors: Ivanov
authors: Université de Rennes 1, INSERM U1099, Laboratoire Traitement du Signal et de l'Image, Rennes, France.
authors: Pascal
authors: P
authors: Benquet
authors: Aix Marseille Université, INSERM UMRS 1106, Institut de Neurosciences des Systèmes, Marseille, France.
authors: Christian-George
authors: CG
authors: Bénar
authors: Sorbonne Universités, UPMC Univ. Paris 06, CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, Paris, France.
authors: Mélanie
authors: M
authors: Pélégrini-Issac
authors: Sorbonne Universités, UPMC Univ. Paris 06, CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, Paris, France.
authors: Habib
authors: H
authors: Benali
authors: Université de Rennes 1, INSERM U1099, Laboratoire Traitement du Signal et de l'Image, Rennes, France.
authors: Fabrice
authors: F
authors: Wendling
mesh_terms: D000200:Action Potentials; D000465:Algorithms; D000818:Animals; D001253:Astrocytes / Q000502:physiology; D001808:Blood Vessels / Q000502:physiology*; D001921:Brain / Q000098:blood supply* / Q000502:physiology*; D002560:Cerebrovascular Circulation; D003198:Computer Simulation; D004195:Disease Models, Animal; D004827:Epilepsy / Q000503:physiopathology; D018698:Glutamic Acid / Q000378:metabolism; D006439:Hemodynamics; D008954:Models, Biological; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018377:Neurotransmitter Agents; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid