Glutamate release from astrocytes as a non-synaptic mechanism for neuronal synchronization in the hippocampus
Introduction
The neuron is traditionally viewed as the functional unit of the nervous system. The brain can thus be regarded as an ensemble of excitatory and inhibitory neurons that are connected dynamically at the synapse. Accordingly, synaptic transmission in the neural network is considered to play a unique, fundamental role in information processing. Recently, however, astrocyte-to-neuron communication has emerged as a novel signalling pathway that uses the same transmitters that mediate the transfer of information between neurons at the synapse (Araque et al., 1999, Carmignoto, 2000, Haydon, 2001, Newman, 2003b, Volterra and Meldolesi, 2005). It has thus been proposed that neurons and astrocytes represent a distinct multifunctional unit in the brain (Fellin and Carmignoto, 2004).
Among the various neuroactive compounds that astrocytes use to signal to neurons, ATP (Coco et al., 2003, Guthrie et al., 1999, Newman, 2003a, Queiroz et al., 1999, Zhang et al., 2003) and the excitatory aminoacid glutamate (Araque et al., 1998, Bezzi et al., 1998, Parpura et al., 1994, Pasti et al., 2001) are certainly the most widely studied. This short review will focus on the most recent findings that provide insights into the functional role that can be ascribed to glutamate of astrocytic origin in the neural network.
Section snippets
Astrocytes signal to neurons at extrasynaptic sites
Astrocyte processes contact a large proportion of the synapses in the hippocampus (Ventura and Harris, 1999). This spatial proximity is functional to a series of important tasks that astrocytes exploit to assist neurons, such as the buffering of extracellular potassium and the uptake (and recycling) of the neurotransmitter glutamate in the vicinity of the synaptic cleft (Bergles et al., 1997, Bergles and Jahr, 1998). However, when dealing with the ability of astrocytic glutamate to activate
Astrocytic glutamate-mediated neuronal synchrony
Pair recording experiments revealed that astrocytic glutamate can activate SICs in the two recorded neurons with a high degree of temporal correlation (Angulo et al., 2004, Fellin et al., 2004). Such a synchronization cannot derive from spreading of the current through gap junctions since depolarizing voltage pulses applied to each neuron of the pair always failed to reveal evidence of electrical coupling between neurons which display synchronized responses (Fellin et al., 2004). Neuronal
Acknowledgements
This work was supported by grants from the Armenise–Harvard University Foundation and the Italian University and Health Ministries to G.C. (FIRB, RBNE01RHZM_003).
References (36)
- et al.
Tripartite synapses: glia, the unacknowledged partner
Trends Neurosci.
(1999) Reciprocal communication systems between astrocytes and neurons
Prog. Neurobiol.
(2000)Glutamate neurotoxicity and diseases of the nervous system
Neuron
(1988)- et al.
Storage and release of ATP from astrocytes in culture
J. Biol. Chem.
(2003) - et al.
Excitatory amino acid receptors in epilepsy
Trends Pharmacol. Sci.
(1990) - et al.
Neuronal synchrony mediated by astrocytic glutamate through activation of extrasynaptic NMDA receptors
Neuron
(2004) - et al.
Astrocytes in kindling: relevance to epileptogenesis
Epilep. Res.
(1996) New roles for astrocytes: regulation of synaptic transmission
Trends Neurosci.
(2003)- et al.
A study of the mechanism of the release of ATP from rat cortical astroglial cells evoked by activation of glutamate receptors
Neuroscience
(1999) Neuronal synchrony: a versatile code for the definition of relations?
Neuron
(1999)