title: Activation of β-adrenergic receptors in rat visual cortex expands astrocytic processes and reduces extracellular space volume.
abstract: Brain extracellular space (ECS) is an interconnected channel that allows diffusion-mediated transport of signaling molecules, metabolites, and drugs. We tested the hypothesis that β-adrenergic receptor (βAR) activation impacts extracellular diffusion-mediated transport of molecules through alterations in the morphology of astrocytes. Two structural parameters of ECS-volume fraction and tortuosity-govern extracellular diffusion. Volume fraction (α) is the volume of ECS relative to the total tissue volume. Tortuosity (λ) is a measure of the hindrance that molecules experience in the ECS, compared to a free medium. The real-time iontophoretic (RTI) method revealed that treatment of acutely prepared visual cortical slices of adult female rats with a βAR agonist, DL-isoproterenol (ISO), decreases α significantly, from 0.22 ± 0.03 (mean ± SD) for controls without agonist to 0.18 ± 0.03 with ISO, without altering λ (control: 1.64 ± 0.04; ISO: 1.63 ± 0.04). Electron microscopy revealed that the ISO treatment significantly increased the cytoplasmic area of astrocytic distal endings per unit area of neuropil by 54%. These findings show that norepinephrine decreases α, in part, through an increase in astrocytic volume following βAR activation. Norepinephrine is recognized to be released within the brain during the awake state and increase neurons' signal-to-noise ratio through modulation of neurons' biophysical properties. Our findings uncover a new mechanism for noradrenergic modulation of neuronal signals. Through astrocytic activation leading to a reduction of α, noradrenergic modulation increases extracellular concentration of neurotransmitters and neuromodulators, thereby facilitating neuronal interactions, especially during wakefulness. Synapse 70:307-316, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York, 11203.|Neural and Behavioral Science Graduate Program, The School of Graduate Studies, State University of New York Downstate Medical Center, Brooklyn, New York, 11203.
authors.forename: Ang Doma
authors.initials: AD
authors.lastname: Sherpa
authors.affiliation: Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York, 11203.
authors.forename: Fanrong
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Herrick High School, New Hyde Park, New York, 11040.
authors.forename: Neethu
authors.initials: N
authors.lastname: Joseph
authors.affiliation: Center for Neural Science, New York University, New York, New York, 10003.
authors.forename: Chiye
authors.initials: C
authors.lastname: Aoki
authors.affiliation: Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York, 11203.|The Robert F. Furchgott Center for Neural and Behavioral Science, State University of New York Downstate Medical Center, Brooklyn, New York, 11203.
authors.forename: Sabina
authors.initials: S
authors.lastname: Hrabetova
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D019581:Neuropil / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D014793:Visual Cortex / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol
keywords: adrenergic system; astrocyte; diffusion; electron microscopy; extracellular space; isoproterenol; real-time iontophoretic method; sleep-wake cycle; tortuosity; volume fraction