Cannabinoid receptors contribute to astroglial Ca2+-signalling and control of synaptic plasticity in the neocortex

Communication between neuronal and glial cells is thought to be very important for many brain functions. Acting via release of gliotransmitters, astrocytes can modulate synaptic strength. The mechanisms underlying ATP release from astrocytes remain uncertain with exocytosis being the most intriguing and debated pathway. We have demonstrated that ATP and d-serine can be released from cortical astrocytes in situ by a SNARE-complex-dependent mechanism. Exocytosis of ATP from astrocytes can activate post-synaptic P2X receptors in the adjacent neurons, causing a downregulation of synaptic and extrasynaptic GABA receptors in cortical pyramidal neurons. We showed that release of gliotransmitters is important for the NMDA receptor-dependent synaptic plasticity in the neocortex. Firstly, induction of long-term potentiation (LTP) by five episodes of theta-burst stimulation (TBS) was impaired in the neocortex of dominant-negative (dn)-SNARE mice. The LTP was rescued in the dn-SNARE mice by application of exogenous non-hydrolysable ATP analogues. Secondly, we observed that weak sub-threshold stimulation (two TBS episodes) became able to induce LTP when astrocytes were additionally activated via CB-1 receptors. This facilitation was dependent on activity of ATP receptors and was abolished in the dn-SNARE mice. Our results strongly support the physiological relevance of glial exocytosis for glia–neuron communications and brain function.

• Publication year

  2014

• Venue

  Philosophical Transactions of the Royal Society B: Biological Sciences

• Publication date

  2014-10-19

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1098/rstb.2014.0077PMID 25225106PMCID 4173298
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Exocytosis of ATP From Astrocytes Modulates Phasic and Tonic Inhibition in the Neocortex

  2014cited by this paper
• The endocannabinoid system and the brain.

  2013cited by this paper
• Endocannabinoid signaling and synaptic function.

  2012cited by this paper
• Astrocyte signaling controls spike timing–dependent depression at neocortical synapses

  2012cited by this paper
• Cannabinoid CB1 receptor deficiency increases contextual fear memory under highly aversive conditions and long-term potentiation in vivo.

  2012cited by this paper
• Contributions of endocannabinoid signaling to psychiatric disorders in humans: genetic and biochemical evidence.

  2012cited by this paper
• Acute cannabinoids impair working memory through astroglial CB1 receptor modulation of hippocampal LTD.

  2012cited by this paper
• Hippocampal endocannabinoids play an important role in induction of long-term potentiation and regulation of contextual fear memory formation.

  2011cited by this paper
• Astrocytes are endogenous regulators of basal transmission at central synapses.

  2011cited by this paper
• Age‐dependent remodelling of ionotropic signalling in cortical astroglia

  2011cited by this paper
• Endocannabinoids potentiate synaptic transmission through stimulation of astrocytes.

  2010cited by this paper
• A Critical Role for α4βδ GABAA Receptors in Shaping Learning Deficits at Puberty in Mice

  2010cited by this paper
• Endocannabinoid-mediated neuron-astrocyte communication

  2009cited by this paper
• Long term potentiation depends on release of D-serine from astrocytes

  2009cited by this paper
• From endocannabinoid profiling to 'endocannabinoid therapeutics'.

  2009cited by this paper
• Astrocytic modulation of sleep homeostasis and cognitive consequences of sleep loss.

  2009cited by this paper
• Roles of Endocannabinoids in Heterosynaptic Long-Term Depression of Excitatory Synaptic Transmission in Visual Cortex of Young Mice

  2008cited by this paper
• Quantal Release of ATP in Mouse Cortex

  2007cited by this paper
• Functional CB1 receptors are broadly expressed in neocortical GABAergic and glutamatergic neurons.

  2007cited by this paper
• Somatodendritic Release of Glutamate Regulates Synaptic Inhibition in Cerebellar Purkinje Cells via Autocrine mGluR1 Activation

  2007cited by this paper
• The tripartite synapse: roles for gliotransmission in health and disease.

  2007cited by this paper
• Temporal and mechanistic dissociation of ATP and adenosine release during ischaemia in the mammalian hippocampus1

  2007cited by this paper
• Endocannabinoid-mediated synaptic plasticity in the CNS.

  2006cited by this paper
• Endocannabinoids restrict hippocampal long-term potentiation via CB1.

  2005cited by this paper
• Astrocytic Purinergic Signaling Coordinates Synaptic Networks

  2005cited by this paper
• Hyperexcitability induced by GABA withdrawal facilitates hippocampal long-term potentiation.

  2004cited by this paper
• Heterosynaptic LTD of hippocampal GABAergic synapses: a novel role of endocannabinoids in regulating excitability.

  2003cited by this paper
• Endocannabinoids facilitate the induction of LTP in the hippocampus

  2002cited by this paper
• Retrograde inhibition of presynaptic calcium influx by endogenous cannabinoids at excitatory synapses onto Purkinje cells.

  2001cited by this paper
• Metabotropic Glutamate Receptors Drive the Endocannabinoid System in Hippocampus

  2001cited by this paper
• Presynaptic specificity of endocannabinoid signaling in the hippocampus.

  2001cited by this paper
• Cannabinoids modulate synaptic strength and plasticity at glutamatergic synapses of rat prefrontal cortex pyramidal neurons.

  2000cited by this paper

• Astroglial CB1 Reveal Sex‐Specific Synaptic Effects of Amphetamine

  2025cites this paper
• Disrupted astrocyte-neuron signaling reshapes brain activity in epilepsy and Alzheimer's disease.

  2025cites this paper
• Concentration-Dependent Bidirectional Modification of Evoked Synaptic Transmission by Gadolinium and Adverse Effects of Gadolinium-Based Contrast Agent

  2025cites this paper
• The effects of cannabinoids on the kidney

  2024cites this paper
• Extracellular glutamate is not modulated by cannabinoid receptor activity

  2024cites this paper
• Astrocyte ryanodine receptors facilitate gliotransmission and astroglial modulation of synaptic plasticity

  2024cites this paper
• Deciphering the astrocytic contribution to learning and relearning

  2024cites this paper
• Astrocyte D1/D5 Dopamine Receptors Govern Non-Hebbian Long-Term Potentiation at Sensory Synapses onto Lamina I Spinoparabrachial Neurons

  2024cites this paper
• Astrocytes enhance plasticity response during reversal learning

  2024cites this paper
• Developmental Spike Timing-Dependent Long-Term Depression Requires Astrocyte d-Serine at L2/3-L2/3 Synapses of the Mouse Somatosensory Cortex

  2024cites this paper
• Human Astrocyte Spheroids as Suitable In Vitro Screening Model to Evaluate Synthetic Cannabinoid MAM2201-Induced Effects on CNS

  2023cites this paper
• Role of the CB2 Cannabinoid Receptor in the Regulation of Food Intake: A Systematic Review

  2023cites this paper
• Interplay Between Astroglial Endocannabinoid System and the Cognitive Dysfunction in Alzheimer's Disease.

  2023cites this paper
• Electrophysiological In Vitro Study of Long‐Range Signal Transmission by Astrocytic Networks

  2023cites this paper
• ATP-mediated signalling in the central synapses.

  2023cites this paper
• Endocannabinoid signaling in astrocytes

  2022cites this paper
• A requirement for astrocyte IP3R2 signaling for whisker experience-dependent depression and homeostatic upregulation in the mouse barrel cortex

  2022cites this paper
• Role for Astrocytes in mGluR-Dependent LTD in the Neocortex and Hippocampus

  2022cites this paper
• Modulation of P2X4 receptor activity by ivermectin and 5‐BDBD has no effect on the development of ARPKD in PCK rats

  2022cites this paper
• Synergy between vesicular and non-vesicular gliotransmission regulates synaptic plasticity and working memory

  2021cites this paper
• Astrocytes as Perspective Targets of Exercise- and Caloric Restriction‐Mimetics

  2021cites this paper
• Astroglial ER-mitochondria calcium transfer mediates endocannabinoid-dependent synaptic integration.

  2021cites this paper
• An astrocytic signaling loop for frequency-dependent control of dendritic integration and spatial learning

  2021influential citation
• The tripartite glutamatergic synapse.

  2021cites this paper
• CB1R-dependent regulation of astrocyte physiology and astrocyte-neuron interactions.

  2021cites this paper
• Astroglia-Derived BDNF and MSK-1 Mediate Experience- and Diet-Dependent Synaptic Plasticity †

  2020cites this paper
• Evidence That Cannabis Exposure, Abuse, and Dependence Are Related to Glutamate Metabolism and Glial Function in the Anterior Cingulate Cortex: A 1H-Magnetic Resonance Spectroscopy Study

  2020cites this paper
• Astrocyte-mediated spike-timing-dependent long-term depression modulates synaptic properties in the developing cortex

  2020cites this paper
• Cannabinoids, Inner Ear, Hearing, and Tinnitus: A Neuroimmunological Perspective

  2020cites this paper
• Fast and Efficient Differentiation of Mouse Embryonic Stem Cells Into ATP-Responsive Astrocytes

  2020cites this paper
• G-Protein-Coupled Receptors in Astrocyte-Neuron Communication.

  2020cites this paper
• Role of astrocyte purinergic signaling in epilepsy

  2019influential citation
• Astrocytic rather than neuronal P2X7 receptors modulate the function of the tri-synaptic network in the rodent hippocampus.

  2019cites this paper
• Melanopsin for precise optogenetic activation of astrocyte‐neuron networks

  2019cites this paper
• Persistent activation of histamine H1 receptors in the hippocampal CA1 region enhances NMDA receptor‐mediated synaptic excitation and long‐term potentiation in astrocyte‐ and D‐serine‐dependent manner

  2019cites this paper
• Extracellular S100β Disrupts Bergman Glia Morphology and Synaptic Transmission in Cerebellar Purkinje Cells

  2019cites this paper
• The plastic d-serine signaling pathway: Sliding from neurons to glia and vice-versa.

  2019cites this paper
• Age- and Experience-Related Plasticity of ATP-Mediated Signaling in the Neocortex

  2019cites this paper
• Astroglia-Derived ATP Modulates CNS Neuronal Circuits.

  2019cites this paper
• Astroglial CB1 Receptors Determine Synaptic D-Serine Availability to Enable Recognition Memory.

  2018cites this paper
• Role for Astroglia-Derived BDNF and MSK1 in Homeostatic Synaptic Plasticity

  2018cites this paper
• Diversity of Astroglial Effects on Aging- and Experience-Related Cortical Metaplasticity

  2018cites this paper
• The Neuroglial Dialog Between Cannabinoids and Hemichannels

  2018cites this paper
• Modulation of Central Synapses by Astrocyte-Released ATP and Postsynaptic P2X Receptors

  2017cites this paper
• Metal ions influx is a double edged sword for the pathogenesis of Alzheimer's disease.

  2017cites this paper
• Chapter 4 – Role for Astroglial α1-Adrenergic receptors in Glia-Neuron Communications and Aging-Related Metaplasticity in the Neocortex

  2017cites this paper
• Linking Mitochondria and Synaptic Transmission: The CB1 Receptor

  2017cites this paper
• Investigating adrenoceptor regulation of the astroglial glycogen reserve

  2017cites this paper
• Exploring the Ca2+-dependent synaptic dynamics in vibro-dissociated cells.

  2017cites this paper
• ATP from synaptic terminals and astrocytes regulates NMDA receptors and synaptic plasticity through PSD-95 multi-protein complex

  2016cites this paper
• A cultura de astrócitos adultos como ferramenta de estudos para compreensão da funcionalidade cerebral

  2016cites this paper
• Physiological Roles of d- Serine in the Central Nervous System

  2016cites this paper
• Astrocytes as new targets to improve cognitive functions.

  2016cites this paper
• Characterization of Amino Acid Profile and Enzymatic Activity in Adult Rat Astrocyte Cultures

  2016cites this paper
• Direct presynaptic and indirect astrocyte-mediated mechanisms both contribute to endocannabinoid signaling in the pedunculopontine nucleus of mice

  2016cites this paper
• Expression and cellular function of vSNARE proteins in brain astrocytes.

  2016cites this paper
• Glia and TRPM2 Channels in Plasticity of Central Nervous System and Alzheimer's Diseases

  2016cites this paper
• Sex Hormones Regulate Cytoskeletal Proteins Involved in Brain Plasticity

  2015cites this paper
• CB1 cannabinoid receptor enrichment in the ependymal region of the adult human spinal cord

  2015cites this paper
• Role for astroglial α1-adrenoreceptors in gliotransmission and control of synaptic plasticity in the neocortex

  2015influential citation
• Role(s) of the mitochondrial type-1 cannabinoid receptor in the brain

  2015cites this paper
• HIV-1, methamphetamine and astrocytes at neuroinflammatory Crossroads

  2015cites this paper
• Brain circuitry outside the synaptic cleft

  2014cites this paper