NYMC Faculty Publications

Astrocytes Release D-Serine by a Large Vesicle

Author Type(s)

Faculty

DOI

10.1016/j.neuroscience.2013.02.029

Journal Title

Neuroscience

First Page

243

Last Page

257

Document Type

Article

Publication Date

6-14-2013

Department

Neurology

Keywords

Adenosine Diphosphate, Animals, Animals, Newborn, Aspartic Acid, Astrocytes, Biophysics, Calcium, Cytoplasmic Vesicles, Dose-Response Relationship, Drug, Electric Stimulation, Excitatory Amino Acid Agents, Excitatory Postsynaptic Potentials, Exocytosis, Female, Glycine, Hippocampus, In Vitro Techniques, Male, Microscopy, Electron, Transmission, Patch-Clamp Techniques, Purinergic P2Y Receptor Antagonists, Rats, Rats, Sprague-Dawley, Serine, Valine

Disciplines

Medicine and Health Sciences | Neurology

Abstract

Long-term potentiation (LTP) of synaptic transmission in the CA1 region of the hippocampus depends on the activation of N-methyl-D-aspartate receptors (NMDARs), which can be regulated by Ca²⁺-dependent release of D-serine from astrocytes. The detailed mechanism underlying astrocytic d-serine release is still unknown. In hippocampal slices prepared from Sprague-Dawley rats, we found that clamping astrocytic [Ca²⁺] at 100-150 nM or puffing artificial cerebrospinal fluid (ACSF) into the extracellular space (weak mechanical stimulation) enhanced the synaptic activation of NMDARs. The enhancement was blocked by the NMDAR glycine site antagonist 5,7-dichlorokynurenic acid, glycine saturation, and infusion of astrocytes with D-amino acid oxidase and the serine racemase inhibitor L-erythro-3-hydroxyaspartate, suggesting the involvement of astrocytic D-serine release. Intracellular 100-150 nM [Ca²⁺] or puffing ACSF stimulated astrocytes to generate D-serine-containing large vesicles (1-3 μm), exocytotic fusion of which released D-serine. The formation of astrocytic large vesicles involved the intracellular fusion of small vesicles and/or other organelles. Spontaneous fusion of large vesicles occurred occasionally in astrocytes at rest, contributing to baseline D-serine levels, which increased the rising slope of NMDAR post-burst potentiation (PBP) without altering the PBP peak amplitude. Thus, under physiological conditions, astrocytic D-serine release by large vesicles facilitated weak theta-burst (TBS consisting of five bursts), but not strong TBS (TBS consisting of 10 bursts) stimulation-induced LTP.

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