Astrocyte and neuron cooperation in long-term depression

To investigate the role of astrocytes in regulating synaptic transmission, we generated inducible transgenic mice that express a dominant-negative SNARE domain selectively in astrocytes to block the release of transmitters from these glial cells. By releasing adenosine triphosphate, which accumulates as adenosine, astrocytes tonically suppressed synaptic transmission, thereby enhancing the dynamic range for long-term potentiation and mediated activity-dependent, heterosynaptic depression. These results indicate that astrocytes are intricately linked in the regulation of synaptic strength and plasticity and provide a pathway for synaptic cross-talk.

LTP and LTD, the long-term potentiation and depression of excitatory synaptic transmission, are widespread phenomena expressed at possibly every excitatory synapse in the mammalian brain. It is now clear that "LTP" and "LTD" are not unitary phenomena. Their mechanisms vary depending on the synapses and circuits in which they operate. Here we review those forms of LTP and LTD for which mechanisms have been most firmly established. Examples are provided that show how these mechanisms can contribute to experience-dependent modifications of brain function.

Long-term depression (LTD) in the CNS has been the subject of intense investigation as a process that may be involved in learning and memory and in various pathological conditions. Several mechanistically distinct forms of this type of synaptic plasticity have been identified and their molecular mechanisms are starting to be unravelled. Most studies have focused on forms of LTD that are triggered by synaptic activation of either NMDARs (N-methyl-D-aspartate receptors) or metabotropic glutamate receptors (mGluRs). Converging evidence supports a crucial role of LTD in some types of learning and memory and in situations in which cognitive demands require a flexible response. In addition, LTD may underlie the cognitive effects of acute stress, the addictive potential of some drugs of abuse and the elimination of synapses in neurodegenerative diseases.