Long term potentiation depends on release of D-serine from astrocytes

By C. Henneberger, Thomas Papouin, Stephane Oliet, Dmitri A. Rusakov. Nature, 2010

1,322 citations recorded by the source corpus.

Long-term potentiation (LTP) of synaptic transmission provides an experimental model for studying mechanisms of memory. The classical form of LTP relies on N-methyl-d-aspartate receptors (NMDARs), and it has been shown that astroglia can regulate their activation through Ca2+-dependent release of the NMDAR co-agonist d-serine. Release of d-serine from glia enables LTP in cultures and explains a correlation between glial coverage of synapses and LTP in the supraoptic nucleus. However, increases in Ca2+ concentration in astroglia can also release other signalling molecules, most prominently glutamate, ATP and tumour necrosis factor-α, whereas neurons themselves can synthesize and supply d-serine. Furthermore, loading an astrocyte with exogenous Ca2+ buffers does not suppress LTP in hippocampal area CA1 (refs 14–16), and the physiological relevance of experiments in cultures or strong exogenous stimuli applied to astrocytes has been questioned. The involvement of glia in LTP induction therefore remains controversial. Here we show that clamping internal Ca2+ in individual CA1 astrocytes blocks LTP induction at nearby excitatory synapses by decreasing the occupancy of the NMDAR co-agonist sites. This LTP blockade can be reversed by exogenous d-serine or glycine, whereas depletion of d-serine or disruption of exocytosis in an individual astrocyte blocks local LTP. We therefore demonstrate that Ca2+-dependent release of d-serine from an astrocyte controls NMDAR-dependent plasticity in many thousands of excitatory synapses nearby.

Subfields: Biochemistry, Cellular and Molecular Neuroscience, Physiology

View Paper: https://www.semanticscholar.org/paper/89d65eed7a229a757c5ec7b91ab31e7b162c37fb

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Citations in the corpus

Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms (2018, background): “In fact, D-serine plays a role in synaptic plasticity (Henneberger et al., 2010), and baseline plasma D-serine levels are negatively correlated with ketamine treatment response in patients suffering from major depression (Moaddel et al.”
Immune modulation of learning, memory, neural plasticity and neurogenesis. (2011, positive): “…cell cultures and slices, the induction of LTP was found to depend on the presence of astrocytes and the secretion of D-serine by these cells, which in turn binds to the glycine-site on neuronal NMDA receptors and enables their critical role in LTP (Henneberger et al., 2010; Yang et al., 2003).”
The Role of Microglia in the Healthy Brain (2011, background): “To functionally test the involvement of astrocytes in this process, we impaired their function using fluoroacetate (FAC), a compound commonly used to block the astrocytic glutamine cycle (Panatier et al., 2006; Henneberger et al., 2010).”
Regulation of extrasynaptic signaling by polysialylated NCAM: Impact for synaptic plasticity and cognitive functions (2017, background): “The binding site for glutamate is located in the GluN2 subunit (Furukawa et al., 2005), whereas glycine and D-serine bind to the strychnine-insensitive NMDAR glycine binding site in theGluN1 subunit of NMDARs.”
Synaptic and extrasynaptic NMDA receptors are gated by different endogenous coagonists. (2012, background): “…633 634 Cell 150, 633–646, August 3, 2012 ª2012 Elsevier Inc. so-called glycine-binding site of NMDAR at several CNS synapses, such as the hippocampus (Henneberger et al., 2010; Mothet et al., 2000; Schell et al., 1995; Yang et al., 2003) the hypothalamus (Panatier et al., 2006), the cortex…”
Chronic Glutamate Toxicity in Neurodegenerative Diseases—What is the Evidence? (2015, background): “Long-term potentiation depends on D-serine release from astrocytes in hippocampal slices, indicating that this amino acid indeed plays an important role in glutamatergic neurotransmission via NMDA receptors (Henneberger et al., 2010).”
Astrocyte-neuron lactate transport is required for long-term memory formation (2011, positive): “However, a growing body of evidence suggests that they play many more active roles, including information processing, signal transmission and regulation of neural and synaptic plasticity (Halassa and Haydon, 2010; Henneberger et al., 2010; Perea et al., 2009).”
Glial fibrillary acidic protein (GFAP) and the astrocyte intermediate filament system in diseases of the central nervous system. (2015, background): “Astrocytes have been shown to be involved in long term potentiation [12], which is important for synaptic plasticity, learning and memory.”