•Astrocytes sense synaptic activity through G protein-coupled receptor activation.•GPCR activation in astrocytes increases their intracellular calcium.•GPCR activation stimulates gliotransmitter ...release from astrocytes.•Gliotransmitters regulate synaptic function by activation of neuronal GPCRs.•GPCR-mediated bidirectional communication astrocyte–neuron regulates behavior.
Astrocytes, a major type of glial cell, are known to play key supportive roles in brain function, contributing to ion and neurotransmitter homeostasis, maintaining the blood–brain barrier and providing trophic and metabolic support for neurons. Besides these support functions, astrocytes are emerging as important elements in brain physiology through signaling exchange with neurons at tripartite synapses. Astrocytes express a wide variety of neurotransmitter transporters and receptors that allow them to sense and respond to synaptic activity. Principal among them are the G-protein-coupled receptors (GPCRs) in astrocytes because their activation by synaptically released neurotransmitters leads to mobilization of intracellular calcium. In turn, activated astrocytes release neuroactive substances called gliotransmitters, such as glutamate, GABA, and ATP/adenosine that lead to synaptic regulation through activation of neuronal GPCRs. In this review we will present and discuss recent evidence demonstrating the critical roles played by GPCRs in the bidirectional astrocyte–neuron signaling, and their crucial involvement in the astrocyte-mediated regulation of synaptic transmission and plasticity.
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
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.
Astrocytes and Behavior Kofuji, Paulo; Araque, Alfonso
Annual review of neuroscience,
07/2021, Volume:
44, Issue:
1
Journal Article
Peer reviewed
Animal behavior was classically considered to be determined exclusively by neuronal activity, whereas surrounding glial cells such as astrocytes played only supportive roles. However, astrocytes are ...as numerous as neurons in the mammalian brain, and current findings indicate a chemically based dialog between astrocytes and neurons. Activation of astrocytes by synaptically released neurotransmitters converges on regulating intracellular Ca
2+
in astrocytes, which then can regulate the efficacy of near and distant tripartite synapses at diverse timescales through gliotransmitter release. Here, we discuss recent evidence on how diverse behaviors are impacted by this dialog. These recent findings support a paradigm shift in neuroscience, in which animal behavior does not result exclusively from neuronal activity but from the coordinated activity of both astrocytes and neurons. Decoding how astrocytes and neurons interact with each other in various brain circuits will be fundamental to fully understanding how behaviors originate and become dysregulated in disease.
•Astrocytes are emerging as important players in synaptic function.•Mechanisms and consequences of astrocyte–neuron signaling is a complex phenomenon.•Astrocyte–neuron signaling is a highly diverse ...phenomenon.•Astrocyte–neuron signaling is a synapse-, cell- and circuit-specific phenomenon.•This diversity and complexity enhances the degrees of freedom of neural circuits.
Astrocytes are emerging as important players in synaptic function, and, consequently, on brain function and animal behavior. According to the Tripartite Synapse concept, astrocytes are integral elements involved in synaptic function. They establish bidirectional communication with neurons, whereby they respond to synaptically released neurotransmitters and, in turn, release gliotransmitters that influence neuronal and synaptic activity. Accumulating evidence is revealing that the mechanisms and functional consequences of astrocyte–neuron signaling are more complex than originally thought. Furthermore, astrocyte–neuron signaling is not based on broad, unspecific interaction; rather, it is a synapse-, cell- and circuit-specific phenomenon that presents a high degree of complexity. This diversity and complexity of astrocyte–synapse interactions greatly enhance the degrees of freedom of the neural circuits and the consequent computational power of the neural systems.
Endocannabinoids and their receptor CB1 play key roles in brain function. Astrocytes express CB1Rs that are activated by endocannabinoids released by neurons. However, the consequences of the ...endocannabinoid-mediated neuron-astrocyte signaling on synaptic transmission are unknown. We show that endocannabinoids released by hippocampal pyramidal neurons increase the probability of transmitter release at CA3-CA1 synapses. This synaptic potentiation is due to CB1R-induced Ca
2+ elevations in astrocytes, which stimulate the release of glutamate that activates presynaptic metabotropic glutamate receptors. While endocannabinoids induce synaptic depression in the stimulated neuron by direct activation of presynaptic CB1Rs, they indirectly lead to synaptic potentiation in relatively more distant neurons by activation of CB1Rs in astrocytes. Hence, astrocyte calcium signal evoked by endogenous stimuli (neuron-released endocannabinoids) modulates synaptic transmission. Therefore, astrocytes respond to endocannabinoids that then potentiate synaptic transmission, indicating that astrocytes are actively involved in brain physiology.
► Endocannabinoids potentiate transmitter release at hippocampal synapses ► The synaptic potentiation requires the stimulation of astrocytes by endocannabinoids ► Astrocytes stimulated by neuronal signals modulate synaptic transmission ► Endocannabinoids depress or potentiate transmission depending on astrocyte activation
While neurons principally mediate brain function, astrocytes are emerging as cells with important neuromodulatory actions in brain physiology. In addition to homeostatic roles, astrocytes respond to ...neurotransmitters with calcium transients stimulating the release of gliotransmitters that regulate synaptic and neuronal functions. We investigated astrocyte-neuronal network interactions in vivo by combining two-photon microscopy to monitor astrocyte calcium and electrocorticogram to record neuronal network activity in the somatosensory cortex during sensory stimulation. We found astrocytes respond to sensory stimuli in a stimulus-dependent manner. Sensory stimuli elicit a surge of neuronal network activity in the gamma range (30-50 Hz) followed by a delayed astrocyte activity that dampens the steady-state gamma activity. This sensory-evoked gamma activity increase is enhanced in transgenic mice with impaired astrocyte calcium signaling and is decreased by pharmacogenetic stimulation of astrocytes. Therefore, cortical astrocytes respond to sensory inputs and regulate sensory-evoked neuronal network activity maximizing its dynamic range.
Astrocytes play active roles in brain physiology. They respond to neurotransmitters and modulate neuronal excitability and synaptic function. However, the influence of astrocytes on synaptic ...transmission and plasticity at the single synapse level is unknown. Ca²⁺ elevation in astrocytes transiently increased the probability of transmitter release at hippocampal area CA3-CA1 synapses, without affecting the amplitude of synaptic events. This form of short-term plasticity was due to the release of glutamate from astrocytes, a process that depended on Ca²⁺ and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein and that activated metabotropic glutamate receptors (mGluRs). The transient potentiation of transmitter release became persistent when the astrocytic signal was temporally coincident with postsynaptic depolarization. This persistent plasticity was mGluR-mediated but N-methyl-D-aspartate receptor-independent. These results indicate that astrocytes are actively involved in the transfer and storage of synaptic information.
Astrocytes are fundamental components of brain information processing and possess the ability to respond to synaptic signaling with increases in cytoplasmic calcium and modulate neuronal activity ...with the subsequent release of neuroactive transmitters. Dopamine signaling is essential for brain physiology and pathology, participating in learning and memory, motor control, neurological diseases, and psychiatric diseases, and astrocytes are emerging as a key cellular target of dopamine signaling. The present review will examine evidence revealing that astrocytes respond to dopamine and modulate information processing in the primary brain regions implicated in the mesolimbic dopamine system. Astrocytes exhibit circuit-specific modulation of neuronal networks and have the potential to serve as a therapeutic target for interventions designed for dopamine pathologies.
Glial cells in neuronal network function Araque, Alfonso; Navarrete, Marta
Philosophical transactions of the Royal Society of London. Series B. Biological sciences,
08/2010, Volume:
365, Issue:
1551
Journal Article
Peer reviewed
Open access
Numerous evidence demonstrates that astrocytes, a type of glial cell, are integral functional elements of the synapses, responding to neuronal activity and regulating synaptic transmission and ...plasticity. Consequently, they are actively involved in the processing, transfer and storage of information by the nervous system, which challenges the accepted paradigm that brain function results exclusively from neuronal network activity, and suggests that nervous system function actually arises from the activity of neuron–glia networks. Most of our knowledge of the properties and physiological consequences of the bidirectional communication between astrocytes and neurons resides at cellular and molecular levels. In contrast, much less is known at higher level of complexity, i.e. networks of cells, and the actual impact of astrocytes in the neuronal network function remains largely unexplored. In the present article, we summarize the current evidence that supports the notion that astrocytes are integral components of nervous system networks and we discuss some functional properties of intercellular signalling in neuron–glia networks.
The term ‘tripartite synapse’ refers to a concept in synaptic physiology based on the demonstration of the existence of bidirectional communication between astrocytes and neurons. Consistent with ...this concept, in addition to the classic ‘bipartite’ information flow between the pre- and postsynaptic neurons, astrocytes exchange information with the synaptic neuronal elements, responding to synaptic activity and, in turn, regulating synaptic transmission. Because recent evidence has demonstrated that astrocytes integrate and process synaptic information and control synaptic transmission and plasticity, astrocytes, being active partners in synaptic function, are cellular elements involved in the processing, transfer and storage of information by the nervous system. Consequently, in contrast to the classically accepted paradigm that brain function results exclusively from neuronal activity, there is an emerging view, which we review herein, in which brain function actually arises from the coordinated activity of a network comprising both neurons and glia.
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