Araque, A., Parpura, V., Sanzgiri, R. P. & Haydon, P. G. Tripartite synapses: glia, the unacknowledged partner. Trends Neurosci. 22, 208–215 (1999).
Araque, A. et al. Gliotransmitters travel in time and space. Neuron 81, 728–739 (2014).
Chung, W. S., Allen, N. J. & Eroglu, C. Astrocytes control synapse formation, function, and elimination. Cold Spring Harb. Perspect. Biol. 7, a020370 (2015).
Savtchouk, I. & Volterra, A. Gliotransmission: beyond black-and-white. J. Neurosci. 38, 14–25 (2018).
Volterra, A., Liaudet, N. & Savtchouk, I. Astrocyte Ca2+ signalling: an unexpected complexity. Nat. Rev. Neurosci. 15, 327–335 (2014).
Sardinha, V. M. et al. Astrocytic signaling supports hippocampal-prefrontal theta synchronization and cognitive function. Glia 65, 1944–1960 (2017).
Adamsky, A. et al. Astrocytic activation generates de novo neuronal potentiation and memory enhancement. Cell 174, 59–71.e14 (2018). Using chemogenetic and optogenetic tools, this study demonstrates that astrocyte stimulation promotes hippocampal long-term synaptic potentiation. Astrocytic activation during memory acquisition is also sufficient to improve memory retrieval, hence proving that astrocytes are capable of producing cognitive-enhancing effects.
Pannasch, U. & Rouach, N. Emerging role for astroglial networks in information processing: from synapse to behavior. Trends Neurosci. 36, 405–417 (2013).
Martín, R., Bajo-Grañeras, R., Moratalla, R., Perea, G. & Araque, A. Circuit-specific signaling in astrocyte-neuron networks in basal ganglia pathways. Science 349, 730–734 (2015).
Mariotti, L. et al. Interneuron-specific signaling evokes distinctive somatostatin-mediated responses in adult cortical astrocytes. Nat. Commun. 9, 82 (2018).
Covelo, A. & Araque, A. Neuronal activity determines distinct gliotransmitter release from a single astrocyte. eLife 7, e32237 (2018).
Bindocci, E. et al. Three-dimensional Ca2+ imaging advances understanding of astrocyte biology. Science 356, eaai8185 (2017).
Stobart, J. L. et al. Cortical circuit activity evokes rapid astrocyte calcium signals on a similar timescale to neurons. Neuron 98, 726–735.e4 (2018).
Wang, X. J. Neurophysiological and computational principles of cortical rhythms in cognition. Physiol. Rev. 90, 1195–1268 (2010).
Kandel, E. R., Dudai, Y. & Mayford, M. R. The molecular and systems biology of memory. Cell 157, 163–186 (2014).
Ghézali, G., Dallérac, G. & Rouach, N. Perisynaptic astroglial processes: dynamic processors of neuronal information. Brain Struct. Funct. 221, 2427–2442 (2016).
Genoud, C. et al. Plasticity of astrocytic coverage and glutamate transporter expression in adult mouse cortex. PLoS Biol. 4, e343 (2006).
Panatier, A. et al. Glia-derived D-serine controls NMDA receptor activity and synaptic memory. Cell 125, 775–784 (2006).
Lushnikova, I., Skibo, G., Muller, D. & Nikonenko, I. Synaptic potentiation induces increased glial coverage of excitatory synapses in CA1 hippocampus. Hippocampus 19, 753–762 (2009).
Sakers, K. et al. Astrocytes locally translate transcripts in their peripheral processes. Proc. Natl Acad. Sci.USA 114, E3830–E3838 (2017).
Bernardinelli, Y. et al. Activity-dependent structural plasticity of perisynaptic astrocytic domains promotes excitatory synapse stability. Curr. Biol. 24, 1679–1688 (2014). This study showed that induction of Ca
transients in astrocytes increases PAP motility and results in enhanced spine stability. Of note, PAPs were activated at individual synapses, resulting in an increased astrocytic coverage and stability of these spines and not of neighboring spines that were contacted by nonactivated PAPs.
Perez-Alvarez, A., Navarrete, M., Covelo, A., Martin, E. D. & Araque, A. Structural and functional plasticity of astrocyte processes and dendritic spine interactions. J. Neurosci. 34, 12738–12744 (2014).
Ostroff, L. E., Manzur, M. K., Cain, C. K. & Ledoux, J. E. Synapses lacking astrocyte appear in the amygdala during consolidation of Pavlovian threat conditioning. J. Comp. Neurol. 522, 2152–2163 (2014).
Pannasch, U. et al. Connexin 30 sets synaptic strength by controlling astroglial synapse invasion. Nat. Neurosci. 17, 549–558 (2014). By using connexin-30-knockout mice, this study found that connexin-30, an astrocyte protein known for its role in gap junctions, is also involved in PAP ensheathment of synapses. Increased synaptic ensheathment is associated with reduced synaptic strength and LTP expression in the hippocampus.
Filosa, A. et al. Neuron-glia communication via EphA4/ephrin-A3 modulates LTP through glial glutamate transport. Nat. Neurosci. 12, 1285–1292 (2009).
Murai, K. K., Nguyen, L. N., Irie, F., Yamaguchi, Y. & Pasquale, E. B. Control of hippocampal dendritic spine morphology through ephrin-A3/EphA4 signaling. Nat. Neurosci. 6, 153–160 (2003).
Tanaka, M. et al. Astrocytic Ca2+ signals are required for the functional integrity of tripartite synapses. Mol. Brain 6, 6 (2013).
Petravicz, J., Boyt, K. M. & McCarthy, K. D. Astrocyte IP3R2-dependent Ca(2+) signaling is not a major modulator of neuronal pathways governing behavior. Front. Behav. Neurosci. 8, 384 (2014).
Henneberger, C., Papouin, T., Oliet, S. H. & Rusakov, D. A. Long-term potentiation depends on release of d-serine from astrocytes. Nature 463, 232–236 (2010).
Yang, Y. et al. Contribution of astrocytes to hippocampal long-term potentiation through release of d-serine. Proc. Natl Acad. Sci. USA 100, 15194–15199 (2003).
Benneyworth, M. A., Li, Y., Basu, A. C., Bolshakov, V. Y. & Coyle, J. T. Cell selective conditional null mutations of serine racemase demonstrate a predominate localization in cortical glutamatergic neurons. Cell. Mol. Neurobiol. 32, 613–624 (2012).
Papouin, T., Dunphy, J. M., Tolman, M., Dineley, K. T. & Haydon, P. G. Septal cholinergic neuromodulation tunes the astrocyte-dependent gating of hippocampal NMDA receptors to wakefulness. Neuron 94, 840–854.e7 (2017). This study shows that astrocyte-derived d-serine levels oscillate according to sleep–wake cycles and this influences learning and memory performance.
Sultan, S. et al. Synaptic integration of adult-born hippocampal neurons is locally controlled by astrocytes. Neuron 88, 957–972 (2015). Using two different approaches to block vesicular release specifically in astrocytes, this study found that d-serine produced by astrocytes enables the unsilencing of new neurons in the adult hippocampus, dendritic spines formation, and their integration in the network. Interestingly, this effect was seen only on dendritic segments that crossed the territories of transgene-expressing astrocytes, indicating a local effect of individual astrocytes.
Toni, N. & Schinder, A. F. Maturation and functional integration of new granule cells into the adult hippocampus. Cold Spring Harb. Perspect. Biol. 8, a018903 (2015).
Pascual, O. et al. Astrocytic purinergic signaling coordinates synaptic networks. Science 310, 113–116 (2005).
Slezak, M. et al. Relevance of exocytotic glutamate release from retinal glia. Neuron 74, 504–516 (2012).
Suzuki, A. et al. Astrocyte-neuron lactate transport is required for long-term memory formation. Cell 144, 810–823 (2011).
Pellerin, L. & Magistretti, P. J. Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc. Natl Acad. Sci. USA 91, 10625–10629 (1994).
Steinman, M. Q., Gao, V. & Alberini, C. M. The role of lactate-mediated metabolic coupling between astrocytes and neurons in long-term memory formation. Front. Integr. Neurosci. 10, 10 (2016).
Clasadonte, J., Scemes, E., Wang, Z., Boison, D. & Haydon, P. G. Connexin 43-mediated astroglial metabolic networks contribute to the regulation of the sleep-wake cycle. Neuron 95, 1365–1380.e5 (2017).
Magistretti, P. J. & Allaman, I. Lactate in the brain: from metabolic end-product to signalling molecule. Nat. Rev. Neurosci. 19, 235–249 (2018).
Herkenham, M. et al. Cannabinoid receptor localization in brain. Proc. Natl Acad. Sci. USA 87, 1932–1936 (1990).
Araque, A., Castillo, P. E., Manzoni, O. J. & Tonini, R. Synaptic functions of endocannabinoid signaling in health and disease. Neuropharmacology 124, 13–24 (2017).
Han, J. et al. Acute cannabinoids impair working memory through astroglial CB1 receptor modulation of hippocampal LTD. cell 148, 1039–1050 (2012).This important study demonstrates that hippocampal LTD occurring upon acute exposure to cannabinoids requires activation of type-1 cannabinoid receptors on astrocytes but not on neurons. This astrocyte-mediated signaling pathway appears to be responsible for the impairment of working memory by marijuana.
Navarrete, M. & Araque, A. Endocannabinoids mediate neuron-astrocyte communication. Neuron 57, 883–893 (2008).
Navarrete, M. & Araque, A. Endocannabinoids potentiate synaptic transmission through stimulation of astrocytes. Neuron 68, 113–126 (2010).
Min, R. & Nevian, T. Astrocyte signaling controls spike timing-dependent depression at neocortical synapses. Nat. Neurosci. 15, 746–753 (2012).
Robin, L. M. et al. Astroglial CB1 receptors determine synaptic d-serine availability to enable recognition memory. Neuron 98, 935–944.e5 (2018).
Gómez-Gonzalo, M. et al. Endocannabinoids induce lateral long-term potentiation of transmitter release by stimulation of gliotransmission. Cereb. Cortex 25, 3699–3712 (2015).
Andrade-Talavera, Y., Duque-Feria, P., Paulsen, O. & Rodríguez-Moreno, A. Presynaptic spike timing-dependent long-term depression in the mouse hippocampus. Cereb. Cortex 26, 3637–3654 (2016).
Pankratov, Y. & Lalo, U. Role for astroglial α1-adrenoreceptors in gliotransmission and control of synaptic plasticity in the neocortex. Front. Cell. Neurosci. 9, 230 (2015).
Navarrete, M. et al. Astrocytes mediate in vivo cholinergic-induced synaptic plasticity. PLoS Biol. 10, e1001259 (2012).
Takata, N. et al. Astrocyte calcium signaling transforms cholinergic modulation to cortical plasticity in vivo. J. Neurosci. 31, 18155–18165 (2011).
Pabst, M. et al. Astrocyte intermediaries of septal cholinergic modulation in the hippocampus. Neuron 90, 853–865 (2016).
Araque, A., Martín, E. D., Perea, G., Arellano, J. I. & Buño, W. Synaptically released acetylcholine evokes Ca2+ elevations in astrocytes in hippocampal slices. J. Neurosci. 22, 2443–2450 (2002).
Lewitus, G. M., Pribiag, H., Duseja, R., St-Hilaire, M. & Stellwagen, D. An adaptive role of TNFα in the regulation of striatal synapses. J. Neurosci. 34, 6146–6155 (2014).
Stellwagen, D. & Malenka, R. C. Synaptic scaling mediated by glial TNF-alpha. Nature 440, 1054–1059 (2006).
Santello, M. & Volterra, A. TNFα in synaptic function: switching gears. Trends Neurosci. 35, 638–647 (2012).
Yang, S., Zhang, L. S., Gibboni, R., Weiner, B. & Bao, S. Impaired development and competitive refinement of the cortical frequency map in tumor necrosis factor-α-deficient mice. Cereb. Cortex 24, 1956–1965 (2014).
Jourdain, P. et al. Glutamate exocytosis from astrocytes controls synaptic strength. Nat. Neurosci. 10, 331–339 (2007).
Santello, M., Bezzi, P. & Volterra, A. TNFα controls glutamatergic gliotransmission in the hippocampal dentate gyrus. Neuron 69, 988–1001 (2011).
Habbas, S. et al. Neuroinflammatory TNFα impairs memory via astrocyte signaling. Cell 163, 1730–1741 (2015). This study identifies a specific astrocytic mechanism linking inflammation to cognitive impairment. Local increase of TNFα in the hippocampal dentate gyrus activates astrocyte TNFR1, which in turn triggers persistent alterations of excitatory synapses. Such synaptic alterations are responsible for the memory deficits displayed by a mouse model of multiple sclerosis.
Buzsáki, G. & Draguhn, A. Neuronal oscillations in cortical networks. Science 304, 1926–1929 (2004).
Paukert, M. et al. Norepinephrine controls astroglial responsiveness to local circuit activity. Neuron 82, 1263–1270 (2014). This interesting study introduces the concept of ‘astrocytic priming’, an increase in astrocyte responsiveness to local network activity according to general behavioral state. In particular, startle behavior triggers simultaneous α-noradrenergic activation of astrocytes in multiple brain regions. As a result, astrocytes in visual cortex respond more to light stimulation.
Perea, G. & Araque, A. Properties of synaptically evoked astrocyte calcium signal reveal synaptic information processing by astrocytes. J. Neurosci. 25, 2192–2203 (2005).
Marshall, L., Helgadóttir, H., Mölle, M. & Born, J. Boosting slow oscillations during sleep potentiates memory. Nature 444, 610–613 (2006).
Poskanzer, K. E. & Yuste, R. Astrocytic regulation of cortical UP states. Proc. Natl Acad. Sci. USA 108, 18453–18458 (2011).
Fellin, T. et al. Endogenous nonneuronal modulators of synaptic transmission control cortical slow oscillations in vivo. Proc. Natl Acad. Sci. USA 106, 15037–15042 (2009).
Poskanzer, K. E. & Yuste, R. Astrocytes regulate cortical state switching in vivo. Proc. Natl Acad. Sci. USA 113, E2675–E2684 (2016).In this seminal study, the authors demonstrate that astrocytic calcium transients promote the switch of the somatosensory cortical circuit to a low-frequency state, a neocortical rhythm important for sleep and memory. Noninvasive activation of astrocytes produces transient increases in extracellular glutamate, which would mediate the cortical state switch.
Tan, Z. et al. Glia-derived ATP inversely regulates excitability of pyramidal and CCK-positive neurons. Nat. Commun. 8, 13772 (2017).
Lee, H. S. et al. Astrocytes contribute to gamma oscillations and recognition memory. Proc. Natl Acad. Sci. USA 111, E3343–E3352 (2014).In this study, the authors specifically induced tetanus toxin expression in astrocytes and found evidence of a reduction in cortical gamma oscillations, which was accompanied by impaired behavioral performance in the novel object recognition test.
Perea, G. et al. Activity-dependent switch of GABAergic inhibition into glutamatergic excitation in astrocyte-neuron networks. eLife 5, e20362 (2016).
Fellin, T. et al. Neuronal synchrony mediated by astrocytic glutamate through activation of extrasynaptic NMDA receptors. Neuron 43, 729–743 (2004).
Sasaki, T., Matsuki, N. & Ikegaya, Y. Action-potential modulation during axonal conduction. Science 331, 599–601 (2011).
Ashhad, S. & Narayanan, R. Active dendrites regulate the impact of gliotransmission on rat hippocampal pyramidal neurons. Proc. Natl Acad. Sci. USA 113, E3280–E3289 (2016).
Bittner, K. C. et al. Conjunctive input processing drives feature selectivity in hippocampal CA1 neurons. Nat. Neurosci. 18, 1133–1142 (2015).
Di Castro, M. A. et al. Local Ca2+ detection and modulation of synaptic release by astrocytes. Nat. Neurosci. 14, 1276–1284 (2011).
Perea, G. & Araque, A. Astrocytes potentiate transmitter release at single hippocampal synapses. Science 317, 1083–1086 (2007).
Chever, O., Dossi, E., Pannasch, U., Derangeon, M. & Rouach, N. Astroglial networks promote neuronal coordination. Sci. Signal. 9, ra6 (2016).
Martin-Fernandez, M. et al. Synapse-specific astrocyte gating of amygdala-related behavior. Nat. Neurosci. 20, 1540–1548 (2017).
Newman, L. A., Korol, D. L. & Gold, P. E. Lactate produced by glycogenolysis in astrocytes regulates memory processing. PLoS One 6, e28427 (2011).
Jensen, C. J. et al. Astrocytic β2 adrenergic receptor gene deletion affects memory in aged mice. PLoS One 11, e0164721 (2016).
Gao, V. et al. Astrocytic β2-adrenergic receptors mediate hippocampal long-term memory consolidation. Proc. Natl Acad. Sci. USA 113, 8526–8531 (2016).This study reports that noradrenaline signaling via β-receptors, which promotes memory consolidation, occurs in astrocytes and requires release of lactate from these cells. Lactate in turn supports the neuronal molecular changes essential for long-term memory formation.
Dong, J. H. et al. Adaptive activation of a stress response pathway improves learning and memory through Gs and β-arrestin-1-regulated lactate metabolism. Biol. Psychiatry 81, 654–670 (2017).
Abel, T., Havekes, R., Saletin, J. M. & Walker, M. P. Sleep, plasticity and memory from molecules to whole-brain networks. Curr. Biol. 23, R774–R788 (2013).
Genzel, L., Kroes, M. C., Dresler, M. & Battaglia, F. P. Light sleep versus slow wave sleep in memory consolidation: a question of global versus local processes? Trends Neurosci. 37, 10–19 (2014).
Norimoto, H. et al. Hippocampal ripples down-regulate synapses. Science 359, 1524–1527 (2018).
Basheer, R., Strecker, R. E., Thakkar, M. M. & McCarley, R. W. Adenosine and sleep-wake regulation. Prog. Neurobiol. 73, 379–396 (2004).
Lalo, U. et al. Exocytosis of ATP from astrocytes modulates phasic and tonic inhibition in the neocortex. PLoS Biol. 12, e1001747 (2014).
Schmitt, L. I., Sims, R. E., Dale, N. & Haydon, P. G. Wakefulness affects synaptic and network activity by increasing extracellular astrocyte-derived adenosine. J. Neurosci. 32, 4417–4425 (2012).
Florian, C., Vecsey, C. G., Halassa, M. M., Haydon, P. G. & Abel, T. Astrocyte-derived adenosine and A1 receptor activity contribute to sleep loss-induced deficits in hippocampal synaptic plasticity and memory in mice. J. Neurosci. 31, 6956–6962 (2011).
Halassa, M. M. et al. Astrocytic modulation of sleep homeostasis and cognitive consequences of sleep loss. Neuron 61, 213–219 (2009). Using dnSNARE mice (see Box 1 for discussion), this study proposes for the first time a key role for adenosine of astrocytic origin in mediating the negative cognitive consequences of sleep deprivation.
Hamby, M. E. et al. Inflammatory mediators alter the astrocyte transcriptome and calcium signaling elicited by multiple G-protein-coupled receptors. J. Neurosci. 32, 14489–14510 (2012).
Teaktong, T. et al. Alzheimer’s disease is associated with a selective increase in alpha7 nicotinic acetylcholine receptor immunoreactivity in astrocytes. Glia 41, 207–211 (2003).
Pirttimaki, T. M. et al. α7 Nicotinic receptor-mediated astrocytic gliotransmitter release: Aβ effects in a preclinical Alzheimer’s mouse model. PLoS One 8, e81828 (2013).
Talantova, M. et al. Aβ induces astrocytic glutamate release, extrasynaptic NMDA receptor activation, and synaptic loss. Proc. Natl Acad. Sci. USA 110, E2518–E2527 (2013).
Lim, D. et al. Amyloid beta deregulates astroglial mGluR5-mediated calcium signaling via calcineurin and Nf-kB. Glia 61, 1134–1145 (2013).
Delekate, A. et al. Metabotropic P2Y1 receptor signalling mediates astrocytic hyperactivity in vivo in an Alzheimer’s disease mouse model. Nat. Commun. 5, 5422 (2014).
Orr, A. G. et al. Astrocytic adenosine receptor A2A and Gs-coupled signaling regulate memory. Nat. Neurosci. 18, 423–434 (2015). Using cell-specific mouse genetics, this study reveals the regulatory role of astrocyte adenosine A
receptor and its downstream Gs-mediated signaling on long-term memory formation. Prominent upregulation of the system in Alzheimer’s disease patients and mouse models would contribute to memory loss.
Hardt, O., Nader, K. & Nadel, L. Decay happens: the role of active forgetting in memory. Trends Cogn. Sci. 17, 111–120 (2013).
Orr, A. G. et al. Istradefylline reduces memory deficits in aging mice with amyloid pathology. Neurobiol. Dis. 110, 29–36 (2018).
Matos, M. et al. Deletion of adenosine A2A receptors from astrocytes disrupts glutamate homeostasis leading to psychomotor and cognitive impairment: relevance to schizophrenia. Biol. Psychiatry 78, 763–774 (2015).
Mitew, S., Kirkcaldie, M. T., Dickson, T. C. & Vickers, J. C. Altered synapses and gliotransmission in Alzheimer’s disease and AD model mice. Neurobiol. Aging 34, 2341–2351 (2013).
Wu, Z., Guo, Z., Gearing, M. & Chen, G. Tonic inhibition in dentate gyrus impairs long-term potentiation and memory in an Alzheimer’s disease model. Nat. Commun. 5, 4159 (2014).
Jo, S. et al. GABA from reactive astrocytes impairs memory in mouse models of Alzheimer’s disease. Nat. Med. 20, 886–896 (2014).
Busche, M. A. & Konnerth, A. Impairments of neural circuit function in Alzheimer’s disease. Phil. Trans. R. Soc. Lond. B 371, 20150429 (2016).
Palop, J. J. & Mucke, L. Amyloid-beta-induced neuronal dysfunction in Alzheimer’s disease: from synapses toward neural networks. Nat. Neurosci. 13, 812–818 (2010).
Li, S. et al. Soluble oligomers of amyloid Beta protein facilitate hippocampal long-term depression by disrupting neuronal glutamate uptake. Neuron 62, 788–801 (2009).
Fogel, H. et al. APP homodimers transduce an amyloid-β-mediated increase in release probability at excitatory synapses. Cell Rep. 7, 1560–1576 (2014).
Verret, L. et al. Inhibitory interneuron deficit links altered network activity and cognitive dysfunction in Alzheimer model. Cell 149, 708–721 (2012).
Kuchibhotla, K. V., Lattarulo, C. R., Hyman, B. T. & Bacskai, B. J. Synchronous hyperactivity and intercellular calcium waves in astrocytes in Alzheimer mice. Science 323, 1211–1215 (2009). By measuring Ca
dynamics in astrocytes in vivo in a mouse model of Alzheimer’s disease, this study was the first to identify a functional alteration (hyperactivity) of glial networks, in complement to the imbalances observed by others in neuronal networks.
Gómez-Gonzalo, M. et al. Neuron-astrocyte signaling is preserved in the aging brain. Glia 65, 569–580 (2017).
Abramov, A. Y., Canevari, L. & Duchen, M. R. Changes in intracellular calcium and glutathione in astrocytes as the primary mechanism of amyloid neurotoxicity. J. Neurosci. 23, 5088–5095 (2003).
Makitani, K., Nakagawa, S., Izumi, Y., Akaike, A. & Kume, T. Inhibitory effect of donepezil on bradykinin-induced increase in the intracellular calcium concentration in cultured cortical astrocytes. J. Pharmacol. Sci. 134, 37–44 (2017).
Reichenbach, N. et al. P2Y1 receptor blockade normalizes network dysfunction and cognition in an Alzheimer’s disease model. J. Exp. Med. 215, 1649–1663 (2018).
Fischer, R., Kontermann, R. E. & Maier, O. Targeting sTNF/TNFR1 signaling as a new therapeutic strategy. Antibodies (Basel) 4, (48–70 (2015).
Cavanagh, C. et al. Inhibiting tumor necrosis factor-α before amyloidosis prevents synaptic deficits in an Alzheimer’s disease model. Neurobiol. Aging 47, 41–49 (2016).
D’Ascenzo, M., Podda, M. V. & Grassi, C. The role of d-serine as co-agonist of NMDA receptors in the nucleus accumbens: relevance to cocaine addiction. Front. Synaptic Neurosci. 6, 16 (2014).
Scofield, M. D. et al. Gq-DREADD selectively initiates glial glutamate release and inhibits cue-induced cocaine seeking. Biol. Psychiatry 78, 441–451 (2015).
Curcio, L. et al. Reduced d-serine levels in the nucleus accumbens of cocaine-treated rats hinder the induction of NMDA receptor-dependent synaptic plasticity. Brain 136, 1216–1230 (2013). In this study, the authors show that cocaine-treated rats present reduced d-serine levels in the nucleus accumbens. This reduction impairs long-term synaptic plasticity, thereby favoring behavioral sensitization to cocaine.
Liu, Z. Q. et al. d-Serine in the nucleus accumbens region modulates behavioral sensitization and extinction of conditioned place preference. Pharmacol. Biochem. Behav. 143, 44–56 (2016).
Hammond, S., Seymour, C. M., Burger, A. & Wagner, J. J. d-Serine facilitates the effectiveness of extinction to reduce drug-primed reinstatement of cocaine-induced conditioned place preference. Neuropharmacology 64, 464–471 (2013).
Kelamangalath, L. & Wagner, J. J. d-Serine treatment reduces cocaine-primed reinstatement in rats following extended access to cocaine self-administration. Neuroscience 169, 1127–1135 (2010).
Seif, T. et al. d-Serine and d-cycloserine reduce compulsive alcohol intake in rats. Neuropsychopharmacology 40, 2357–2367 (2015).
Wu, J., Zhao, R., Guo, L. & Zhen, X. Morphine-induced inhibition of Ca2+ -dependent d-serine release from astrocytes suppresses excitability of GABAergic neurons in the nucleus accumbens. Addict. Biol. 22, 1289–1303 (2017).
Boury-Jamot, B. et al. Disrupting astrocyte-neuron lactate transfer persistently reduces conditioned responses to cocaine. Mol. Psychiatry 21, 1070–1076 (2016).
Zhang, Y. et al. Inhibition of lactate transport erases drug memory and prevents drug relapse. Biol. Psychiatry 79, 928–939 (2016).
Panatier, A. Astrocytes are endogenous regulators of basal transmission at central synapses. Cell 146, 785–798 (2011).
Halassa, M. M., Fellin, T., Takano, H., Dong, J. H. & Haydon, P. G. Synaptic islands defined by the territory of a single astrocyte. J. Neurosci. 27, 6473–6477 (2007).
Fields, R. D. et al. Glial biology in learning and cognition. Neuroscientist 20, 426–431 (2014).
Porto-Pazos, A. B. et al. Artificial astrocytes improve neural network performance. PLoS One 6, e19109 (2011).
Amiri, M., Hosseinmardi, N., Bahrami, F. & Janahmadi, M. Astrocyte- neuron interaction as a mechanism responsible for generation of neural synchrony: a study based on modeling and experiments. J. Comput. Neurosci. 34, 489–504 (2013).
Tewari, S. & Parpura, V. A possible role of astrocytes in contextual memory retrieval: An analysis obtained using a quantitative framework. Front. Comput. Neurosci. 7, 145 (2013).
Agulhon, C., Fiacco, T. A. & McCarthy, K. D. Hippocampal short- and long-term plasticity are not modulated by astrocyte Ca2+ signaling. Science 327, 1250–1254 (2010).
Otte, D. M. et al. Effects of chronic d-serine elevation on animal models of depression and anxiety-related behavior. PLoS One 8, e67131 (2013).
Chen, N. et al. Nucleus basalis-enabled stimulus-specific plasticity in the visual cortex is mediated by astrocytes. Proc. Natl Acad. Sci. USA 109, E2832–E2841 (2012).
Saab, A. S. et al. Bergmann glial AMPA receptors are required for fine motor coordination. Science 337, 749–753 (2012).
Fiacco, T. A. et al. Selective stimulation of astrocyte calcium in situ does not affect neuronal excitatory synaptic activity. Neuron 54, 611–626 (2007).
Fujita, T. et al. Neuronal transgene expression in dominant-negative SNARE mice. J. Neurosci. 34, 16594–16604 (2014).
Chai, H. et al. Neural circuit-specialized astrocytes: transcriptomic, proteomic, morphological, and functional evidence. Neuron 95, 531–549.e9 (2017).
Sharma, K. et al. Cell type- and brain region-resolved mouse brain proteome. Nat. Neurosci. 18, 1819–1831 (2015).
Jahn, H. M., Scheller, A. & Kirchhoff, F. Genetic control of astrocyte function in neural circuits. Front. Cell. Neurosci. 9, 310 (2015).
Hirrlinger, P. G., Scheller, A., Braun, C., Hirrlinger, J. & Kirchhoff, F. Temporal control of gene recombination in astrocytes by transgenic expression of the tamoxifen-inducible DNA recombinase variant CreERT2. Glia 54, 11–20 (2006).
Srinivasan, R. et al. New transgenic mouse lines for selectively targeting astrocytes and studying calcium signals in astrocyte processes in situ and in vivo. Neuron 92, 1181–1195 (2016).
Winchenbach, J. et al. Inducible targeting of CNS astrocytes in Aldh1l1-CreERT2 BAC transgenic mice. F1000Res. 5, 2934 (2016).
Metzger, D., Clifford, J., Chiba, H. & Chambon, P. Conditional site-specific recombination in mammalian cells using a ligand-dependent chimeric Cre recombinase. Proc. Natl Acad. Sci. USA 92, 6991–6995 (1995).
Sauer, B. & Henderson, N. Site-specific DNA recombination in mammalian cells by the Cre recombinase of bacteriophage P1. Proc. Natl Acad. Sci. USA 85, 5166–5170 (1988).
Gossen, M. & Bujard, H. Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc. Natl Acad. Sci. USA 89, 5547–5551 (1992).
Gebara, E. et al. Heterogeneity of radial glia-like cells in the adult hippocampus. Stem Cells 34, 997–1010 (2016).
Mori, T. et al. Inducible gene deletion in astroglia and radial glia--a valuable tool for functional and lineage analysis. Glia 54, 21–34 (2006).