A2A‐D2 receptor–receptor interaction modulates gliotransmitter release from striatal astrocyte processes

Abstract

Accumulating evidence indicates that astrocytes are actively involved in brain function by regulating synaptic activity and plasticity. Different gliotransmitters, such as glutamate, ATP, GABA or D-serine, released form astrocytes have been shown to induce different forms of synaptic regulation. However, whether a single astrocyte may release different gliotransmitters is unknown. Here we show that mouse hippocampal astrocytes activated by endogenous (neuron-released endocannabinoids or GABA) or exogenous (single astrocyte Ca 2+ uncaging) stimuli modulate putative single CA3-CA1 hippocampal synapses. The astrocyte-mediated synaptic modulation was biphasic and consisted of an initial glutamate-mediated potentiation followed by a purinergic-mediated depression of neurotransmitter release. The temporal dynamic properties of this biphasic synaptic regulation depended on the firing frequency and duration of the neuronal activity that stimulated astrocytes. Present results indicate that single astrocytes can decode neuronal activity and, in response, release distinct gliotransmitters to differentially regulate neurotransmission at putative single synapses.

Near‐infrared laser photons induce glutamate release from cerebrocortical nerve terminals

“…We monitored the release of a neurotransmitter from a synaptosomal monolayer, or of a gliotransmitter from a gliosomal monolayer, by removing any active substance that might be released, thereby avoiding indirect effects (see ). As this approach enable us to study the direct effects of substances on transmitter release , it appears suitable for the study of the direct effects of a physical stimulus (eg, laser light) on transmitter release.…”

“…Nerve terminals prepared from CNS regions preserve the features of presynaptic terminals in situ, including their mitochondrial function (see and references therein), and can release glutamate in a vesicular way (see and references therein). In addition, astrocyte processes prepared from the adult rodent CNS, which reflect the behavior of the processes in mature neuron‐astrocyte networks, are capable of exocytotic release of glutamate (see and references therein).…”

“…Regarding the mechanisms that might be involved in the ability of photons to evoke glutamate exocytosis, it should be noted that mitochondria and ATP production are widely recognized targets for PBM (see and references therein), and that presynaptic mitochondria and their capacity for ATP production are known to be related to the efficiency of synaptic vesicle exocytosis . Notably, we obtained ultrastructural evidence that synaptosomes from the rodent CNS are equipped with presynaptic mitochondria, while gliosomes are not (see ). Although activation of mitochondrial ATP production might be related to the glutamate‐releasing effect of photons, further investigation is required for a better understanding of the ability of photons to activate vesicular glutamate release from nerve endings.…”

“…Cerebrocortical purified nerve terminals (synaptosomes) and astrocyte processes (gliosomes) were prepared as previously described . Briefly, the tissue was homogenized in Tris‐buffered sucrose (pH 7.4) and centrifuged; the supernatant was stratified on a discontinuous Percoll gradient (2%, 6%, 10%, 20% [vol/vol] in Tris‐buffered sucrose) and centrifuged.…”

GLIA Porto 2019: Abstracts Oral Presentations, Posters, Indexes

“…On gliosomes, we obtained evidence of the A2A-D2 RRI, by assessing the interference by the synthetic peptide VLRRRRKRVN (corresponding to the D2 region involved in electrostatic interaction underlying A2A-D2 heterodimerization) or intracytoplasmic homocysteine (Cervetto et al, 2017;. Previously, we focused our attention on glutamate release and the modulation mediated by A2A and D2 receptors.…”