Heterosynaptic long-term depression mediated by ATP released from astrocytes
Glia. 2012 Oct 8;
Chen J, Tan Z, Zeng L, Zhang X, He Y, Gao W, Wu X, Li Y, Bu B, Wang W, Duan S
Abstract
Heterosynaptic long-term depression (hLTD) at untetanized synapses accompanying the induction of long-term potentiation (LTP) spatially sharpens the activity-induced synaptic potentiation; however, the underlying mechanism remains unclear.
We found that hLTD in the hippocampal CA1 region is caused by stimulation-induced ATP release from astrocytes that suppresses transmitter release from untetanized synaptic terminals via activation of P2Y receptors.
Selective stimulation of astrocytes expressing channel rhodopsin-2, a light-gated cation channel permeable to Ca(2+) , resulted in LTD of synapses on neighboring neurons. This synaptic modification required Ca(2+) elevation in astrocytes and activation of P2Y receptors, but not N-methyl-D-aspartate receptors.
Furthermore, blocking P2Y receptors or buffering astrocyte intracellular Ca(2+) at a low level prevented hLTD without affecting LTP induced by SC stimulation.
Thus, astrocyte activation is both necessary and sufficient for mediating hLTD accompanying LTP induction, strongly supporting the notion that astrocytes actively participate in activity-dependent synaptic plasticity of neural circuits.
PMID: 23044720
Adenosine triphosphate, (ATP), is energy-carrying molecule formed in the cells of all living things. It contains three components: Adenine (a nucleic acid), Ribose (a sugar), and a chain of 3 Phosphate groups.
Ribose is a sugar formed from glucose.
Adenine, a nucleic acid also used to form DNA, was called in the past Vitamin B4, though it is no longer considered a true vitamin. Adenine is formed through a complex pathway involving glucose, glycine, glutamine, aspartic acid, and folic acid.
Adenosine is the molecular combination of Adenine and Ribose.
The Phophate groups are where the energy is stored. Through a process called phosphorylation, the phophate group is transferred from ATP by enzymes to release the energy contained.
Cells of the human body break down food molecules and store the energy they contain temporarily as ATP. ATP is then used to provide energy to other cellular processes. These cellular processes include chemical reactions that require an input of energy, active transport of molecules across cell membranes, mechanical work such as muscle contraction.
ATP is also the most commonly used signal in the nervous system. Whenever neurons are activated, ATP is released along with other neurotransmitters. Neurons also release ATP throughout their axons via ion channels when the neuron expels fluids and ions brought in by the passing electrochemical current. The ATP released stimulates astrocytes and oligrodendrocytes, informing them that the neuron was activated.
ATP also is released by astrocytes and other glial cells as a signal to control neuron activity.
Adenosine is a byproduct of using ATP for energy. Adenosine is also an inhibitory neurotransmitter.
Caffeine blocks adenosine receptors. This shifts the balance of signaling to stimulant neurotransmitters. In this way, caffeine is an anti-calming agent rather than stimulant.
Calcium is a mineral that is used as a signal used by glial calls.
This synaptic modification required Ca(2+) elevation in astrocytes and activation of P2Y receptors, but not N-methyl-D-aspartate receptors.