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Original Article

Exp Neurobiol 2019; 28(1): 30-42

Published online February 28, 2019

© The Korean Society for Brain and Neural Sciences

Pharmacological Dissection of Intrinsic Optical Signal Reveals a Functional Coupling between Synaptic Activity and Astrocytic Volume Transient

Junsung Woo1,†, Young-Eun Han1,2,3,†, Wuhyun Koh1,2,3, Joungha Won1,3,4, Min Gu Park1,3,5, Heeyoung An1,3,5, and C. Justin Lee1,2,3*

1Center for Glia-Neuron Interaction, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.

2Department of Neuroscience, Division of Bio-medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Korea.

3Center for Cognition and Sociality, Institute for Basic Science (IBS), Daejeon 34126, Korea.

4Department of Biological Sciences, Korea Advanced Institutes of Science and Technology (KAIST), Daejeon 34141, Korea.

5KU-KIST, Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Korea.

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-42-878-9150, FAX: 82-42-878-9151
These authors are contributed equally to this work.

Received: January 27, 2019; Revised: February 12, 2019; Accepted: February 14, 2019

The neuronal activity-dependent change in the manner in which light is absorbed or scattered in brain tissue is called the intrinsic optical signal (IOS), and provides label-free, minimally invasive, and high spatial (~100 µm) resolution imaging for visualizing neuronal activity patterns. IOS imaging in isolated brain slices measured at an infrared wavelength (>700 nm) has recently been attributed to the changes in light scattering and transmittance due to aquaporin-4 (AQP4)-dependent astrocytic swelling. The complexity of functional interactions between neurons and astrocytes, however, has prevented the elucidation of the series of molecular mechanisms leading to the generation of IOS. Here, we pharmacologically dissected the IOS in the acutely prepared brain slices of the stratum radiatum of the hippocampus, induced by 1 s/20 Hz electrical stimulation of Schaffer-collateral pathway with simultaneous measurement of the activity of the neuronal population by field potential recordings. We found that 55% of IOSs peak upon stimulation and originate from postsynaptic AMPA and NMDA receptors. The remaining originated from presynaptic action potentials and vesicle fusion. Mechanistically, the elevated extracellular glutamate and K+ during synaptic transmission were taken up by astrocytes via a glutamate transporter and quinine-sensitive K2P channel, followed by an influx of water via AQP-4. We also found that the decay of IOS is mediated by the DCPIB- and NPPB-sensitive anion channels in astrocytes. Altogether, our results demonstrate that the functional coupling between synaptic activity and astrocytic transient volume change during excitatory synaptic transmission is the major source of IOS.

Graphical Abstract

Keywords: Intrinsic optical signal, Astrocyte volume, K2P channel, NPPB-sensitive anion channel, Activity-dependent astrocyte volume change