Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/4693
Title: | Different cellular sources and different roles of adenosine: A1 receptor-mediated inhibition through astrocytic-driven volume transmission and synapse-restricted A2A receptor-mediated facilitation of plasticity | Authors: | Cunha, Rodrigo A. | Keywords: | Adenosine; A1 receptor; A2A receptor; Nerve ending; Nerve terminal; Astrocyte; Synaptic plasticity; Modulation | Issue Date: | 2008 | Citation: | Neurochemistry International. 52:1-2 (2008) 65-72 | Abstract: | Adenosine is a prototypical neuromodulator, which mainly controls excitatory transmission through the activation of widespread inhibitory A1 receptors and synaptically located A2A receptors. It was long thought that the predominant A1 receptor-meditated modulation by endogenous adenosine was a homeostatic process intrinsic to the synapse. New studies indicate that endogenous extracellular adenosine is originated as a consequence of the release of gliotransmitters, namely ATP, which sets a global inhibitory tonus in brain circuits rather than in a single synapse. Thus, this neuron-glia long-range communication can be viewed as a form of non-synaptic transmission (a concept introduced by Professor Sylvester Vizi), designed to reduce noise in a circuit. This neuron-glia-induced adenosine release is also responsible for exacerbating salient information through A1 receptor-mediated heterosynaptic depression, whereby the activation of a particular synapse recruits a neuron-glia network to generate extracellular adenosine that inhibits neighbouring non-tetanised synapses. In parallel, the local activation of facilitatory A2A receptors by adenosine, formed from ATP released only at high frequencies from neuronal vesicles, down-regulates A1 receptors and facilitates plasticity selectively in the tetanised synapse. Thus, upon high-frequency firing of a given pathway, the combined exacerbation of global A1 receptor-mediated inhibition in the circuit (heterosynaptic depression) with the local synaptic activation of A2A receptors in the activated synapse, cooperate to maximise salience between the activated and non-tetanised synapses. | URI: | https://hdl.handle.net/10316/4693 | DOI: | 10.1016/j.neuint.2007.06.026 | Rights: | openAccess |
Appears in Collections: | FMUC Medicina - Artigos em Revistas Internacionais |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
filee3d89c7cd9a046c8bfb54185ac1e20e8.pdf | 387.8 kB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.