Please use this identifier to cite or link to this item: http://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: http://hdl.handle.net/10316/4693
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais

Files in This Item:
File Description SizeFormat
filee3d89c7cd9a046c8bfb54185ac1e20e8.pdf387.8 kBAdobe PDFView/Open
Show full item record

Page view(s) 50

368
checked on Dec 2, 2019

Download(s)

175
checked on Dec 2, 2019

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.