Astrocytes play a critical role in transient heterosynaptic depression in the rat hippocampal CA1 region

Abstract

Active synapses can reduce the probability of transmitter release at neighbouring synapses. Depending on whether such heterosynaptic depression is mediated by intersynaptic diffusion of transmitter or by release of gliotransmitters, astrocytes should either hinder or promote the heterosynaptic depression. In the present study we have examined the developmental profile and astrocytic involvement in a transient heterosynaptic depression (tHeSD) in the CA1 region of the rat hippocampal slice preparation. A short stimulus burst (3 impulses at 50 Hz) to one group of synapses elicited a depression of the field EPSP evoked in another group of synapses that amounted to about 25% 0.5 s after the conditioning burst. This tHeSD was associated with an increase in the paired-pulse ratio of about 30%. The tHeSD was not present in slices from rats younger than 10 postnatal days and developed towards the adult magnitude between postnatal days 10 and 20. The tHeSD was totally prevented by the glia-specific toxin fluoroacetate (FAC), by carbenoxolone, a general blocker of connexin-based channels, and by endothelin, an endogenous peptide that has been shown to block astrocytic connexin-based channels. Antagonists to GABA B receptors and group II/III metabotropic glutamate receptors (mGluRs) abolished the tHeSD whereas antagonists to NMDA-and adenosine A1 receptors, and to group I mGluRs, did not affect the tHeSD. These results suggest that the tHeSD relies on GABA B receptors, group II/III mGluRs and on gliotransmitter release from functionally mature astrocytes.

Astrocytes Impose Postburst Depression of Release Probability at Hippocampal Glutamate Synapses

“…By responding to presynaptically released glutamate and by releasing gliotransmitters, the astrocyte part of the tripartite synapse is strategically positioned to modulate release probability in an activity-dependent manner (Newman, 2003). Indeed, several studies have shown that gliotransmitters can modulate release probability at cortical synapses (Robitaille, 1998;Serrano et al, 2006;Zhang et al, 2003;Liu et al, 2004;Pascual et al, 2005;Andersson et al, 2007;Jourdain et al, 2007), and we now show that astrocytes play an active role in mediating homosynaptic short-term synaptic depression.…”

“…2 A), emerging at postnatal day 10 and being fully developed at postnatal day 20, would thus be more consistent with activity-induced release of gliotransmitters from astrocytes than with spillover. To more directly test whether the PBD required some form of astrocyte signaling, we elicited the PBD before and after the application of the glial metabolic inhibitor FAc (Fonnum et al, 1997;Andersson et al, 2007). Consistent with a critical role for astrocyte signaling, FAc completely blocked the PBD (Fig.…”

“…Since astrocyte function and morphology develop during an extended postnatal period (Konietzko and Muller, 1994;Bushong et al, 2004;Schools et al, 2006;Andersson et al, 2007), activityinduced release of gliotransmitters from astrocytes would be expected to increase with development. Spillover, on the other hand, would rather be expected to be favored early in development when astrocyte processes around synapses and glutamate uptake are poorly developed (Piet et al, 2004;Diamond, 2005).…”

Loss of IP3Receptor-Dependent Ca2+Increases in Hippocampal Astrocytes Does Not Affect Baseline CA1 Pyramidal Neuron Synaptic Activity

“…Astrocytes have been reported recently to have a functional role in neuronal excitability (Araque et al, 1998a;Haydon and Carmignoto, 2006), heterosynaptic depression (Pascual et al, 2005;Serrano et al, 2006;Andersson et al, 2007), cerebrovascular dynamics (Zonta et al, 2003;Straub and Nelson, 2007), and pathological states such as epilepsy Tian et al, 2005;Fellin et al, 2006a). One unifying feature of these findings is that astrocyte modulation of these processes occurs via a Ca 2ϩ -dependent release of "gliotransmitters," including ATP (which is converted to adenosine by ectonucleotidases) and glutamate (Montana et al, 2006).…”

Integrated Brain Circuits: Neuron-Astrocyte Interaction in Sleep-Related Rhythmogenesis

“…Later studies demonstrated that this process can be observed in acute brain slices[71,72,73,74,75,76,77,78,79] and in vivo [80]. Astrocytes were later shown to release a number of chemical transmitters, including ATP[81,82,83,84,85], D-serine[86,87,88,89], TNF-alpha[90,91], and ANP[92], in a process that has recently been termed gliotransmission[93]. Based on the early studies of gliotransmission, the concept of the tripartite synapse was proposed[94], highlighting the role of the astrocyte as a third active element in information processing at the synapse[95,96,97,98,99].…”