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Astrocytes release D-serine by a large vesicle
1Department of Cell Biology and Anatomy, New York Medical College, Basic Science Building, Room 220, Valhalla, NY 10595, USA.
Neuroscience
|March 15, 2013
Summary
Astrocytes release D-serine via large vesicles, enhancing N-methyl-D-aspartate receptor (NMDAR) activation and synaptic plasticity. This mechanism is crucial for certain forms of long-term potentiation (LTP) in the hippocampus.
Area of Science:
- Neuroscience
- Cellular Biology
- Synaptic Plasticity
Background:
- Long-term potentiation (LTP) in the hippocampus CA1 region is N-methyl-D-aspartate receptor (NMDAR) dependent.
- Astrocytic D-serine regulates NMDARs, but the release mechanism remains unclear.
- Ca²⁺ signaling in astrocytes plays a role in modulating synaptic transmission.
Purpose of the Study:
- To elucidate the mechanism of D-serine release from astrocytes.
- To investigate the role of astrocytic D-serine in NMDAR activation and hippocampal LTP.
- To understand the formation and function of astrocytic vesicles involved in D-serine release.
Main Methods:
- Experiments conducted on Sprague-Dawley rat hippocampal slices.
- Manipulation of astrocytic intracellular calcium ([Ca²⁺]) levels (100-150 nM).
- Application of artificial cerebrospinal fluid (ACSF) via puffing (weak mechanical stimulation).
- Pharmacological inhibition of NMDARs (glycine site antagonist), D-serine synthesis (serine racemase inhibitor), and D-serine degradation (D-amino acid oxidase).
- Analysis of vesicle formation, fusion, and D-serine release using microscopy and electrophysiology.
Main Results:
- Elevated astrocytic [Ca²⁺] or weak mechanical stimulation enhanced NMDAR activation.
- These effects were blocked by NMDAR antagonists, glycine saturation, and inhibitors of D-serine metabolism, confirming astrocytic D-serine involvement.
- Astrocytes formed large D-serine-containing vesicles (1-3 μm) through intracellular fusion, releasing D-serine via exocytosis.
- Spontaneous vesicle fusion contributed to baseline D-serine, affecting NMDAR post-burst potentiation (PBP) slope but not peak.
- Astrocytic D-serine release facilitated weak theta-burst stimulation (TBS)-induced LTP but not strong TBS-induced LTP.
Conclusions:
- Astrocytes release D-serine through the exocytosis of large vesicles, a process regulated by intracellular calcium.
- This astrocytic D-serine release mechanism is critical for modulating NMDAR function and facilitating specific forms of hippocampal LTP.
- The findings reveal a novel pathway for glial regulation of synaptic plasticity under physiological conditions.
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