Heterosynaptic long‐term depression mediated by ATP released from astrocytes

Chen, Jiadong; Tan, Zhibing; Zeng, Li; Zhang, Xiaoxing; He, Yu; Gao, Wei; Wu, Xiumei; Li, Yuju; Bu, Bitao; Wang, Wei; Duan, Shumin

doi:10.1002/glia.22425

Cited by 128 publications

(144 citation statements)

References 57 publications

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“…Unlike the homosynaptic LTP, the heterosynaptic LTD displayed a decrease in CV −2 and an increase in PPR (Fig. 3D), which supported for a decreased p r as the basis for the synaptic depression, in agreement with previous reports (14,25,26). Importantly, dialyzing the postsynaptic neuron with BAPTA fully blocked the homosynaptic LTP (−8.8 ± 7.7%; Fig.…”

Section: Activity-dependent Coordinated Modulation Of Presynaptic Strsupporting

confidence: 91%

“…Moreover, astrocytes are coupled to each other through gap junctions, and by forming a network, they are thought to be capable of modulating the efficacy of a population of synapses by coordinately releasing diffusible gliotransmitters such as glutamate, endocannabinoids, ATP or D-serine that target synaptic receptors (15,16). In the hippocampus, astrocytes respond to Schaffer collateral stimulations (14,(22)(23)(24), and they mediate tetanus-induced heterosynaptic presynaptic LTD at CA1 synapses through purinergic signaling (14,(25)(26)(27). The involvement of astrocytes in heterosynaptic depression of nonstimulated inputs raises the intriguing possibility that astrocytes might actively play a role in balancing synaptic strengths between different inputs.…”

Section: +mentioning

confidence: 99%

“…Therefore, heterosynaptic presynaptic plasticity in our culture system appears not to require postsynaptic Ca 2+ . We next examined a role for NMDARs and astrocytes that had been previously shown to mediate heterosynaptic LTD at hippocampal CA3-CA1 synapses (14,(25)(26)(27)39). Despite the apparent lack of requirement for postsynaptic Ca We also tested a possible role for L-VGCCs.…”

Section: Activity-dependent Coordinated Modulation Of Presynaptic Strmentioning

confidence: 99%

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Astrocytes regulate heterogeneity of presynaptic strengths in hippocampal networks

Letellier

Park

Chater

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

117

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Dendrites are neuronal structures specialized for receiving and processing information through their many synaptic inputs. How input strengths are modified across dendrites in ways that are crucial for synaptic integration and plasticity remains unclear. We examined in single hippocampal neurons the mechanism of heterosynaptic interactions and the heterogeneity of synaptic strengths of pyramidal cell inputs. Heterosynaptic presynaptic plasticity that counterbalances input strengths requires N-methyl-D-aspartate receptors (NMDARs) and astrocytes. Importantly, this mechanism is shared with the mechanism for maintaining highly heterogeneous basal presynaptic strengths, which requires astrocyte Ca 2+ signaling involving NMDAR activation, astrocyte membrane depolarization, and L-type Ca 2+ channels. Intracellular infusion of NMDARs or Ca 2+-channel blockers into astrocytes, conditionally ablating the GluN1 NMDAR subunit, or optogenetically hyperpolarizing astrocytes with archaerhodopsin promotes homogenization of convergent presynaptic inputs. Our findings support the presence of an astrocytedependent cellular mechanism that enhances the heterogeneity of presynaptic strengths of convergent connections, which may help boost the computational power of dendrites.synapse heterogeneity | synaptic strength | astrocyte | hippocampal neuron | heterosynaptic plasticity A n enduring challenge in neurobiology is to understand how neurons set the strengths of their numerous synapses to efficiently process and store different information while maintaining network homeostasis. Electrophysiology and imaging approaches have revealed that synapses display a high degree of functional heterogeneity, even for those sharing the same axon or dendrite (1-3). The observation that synaptic strengths are heterogeneous, in turn, suggests that synapses can operate independently from one another. Accordingly, many studies have demonstrated the input-specificity of Hebbian and also of homeostatic forms of synaptic plasticity, where synaptic changes are restricted to inputs whose activity is altered (4-6). Nevertheless, such a synapse-autonomous behavior could potentially compromise the global network homeostasis by biasing the overall activity toward excitation or depression, and to overcome this issue, it has been proposed that distinct inputs cooperate by coordinating their relative strengths through heterosynaptic interactions (7-9). In support of the idea that synapses behave as interdependent rather than isolated functional units, the restriction of synaptic strength changes to active inputs has been demonstrated to break down at times, with the induction of synaptic plasticity in the stimulated input accompanying either synaptic depression or potentiation of the nonstimulated inputs (10-13). In a highly studied plasticity paradigm of long-term potentiation (LTP) at hippocampal Schaffer collateral-CA1 synapses, tetanic stimulation that induces LTP is often accompanied by presynaptic long-term depression (LTD) of nonstimulated Schaffer collat...

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Section: Activity-dependent Coordinated Modulation Of Presynaptic Strsupporting

confidence: 91%

Section: +mentioning

confidence: 99%

Section: Activity-dependent Coordinated Modulation Of Presynaptic Strmentioning

confidence: 99%

See 1 more Smart Citation

Astrocytes regulate heterogeneity of presynaptic strengths in hippocampal networks

Letellier

Park

Chater

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

117

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“…Spread of depression could be mediated by diffusion of LTD-specific signaling molecules (e.g., calcineurin and protein phosphatase 1) through the dendrite into neighboring spines (45). Alternatively, astrocytes could mediate heterosynaptic LTD (46). Subsequently, the weakened synapses might more likely be eliminated.…”

Section: Discussionmentioning

confidence: 99%

Long-term depression triggers the selective elimination of weakly integrated synapses

Wiegert

Oertner

2013

Proc. Natl. Acad. Sci. U.S.A.

113

117

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Long-term depression (LTD) weakens synaptic transmission in an activity-dependent manner. It is not clear, however, whether individual synapses are able to maintain a depressed state indefinitely, as intracellular recordings rarely exceed 1 h. Here, we combine optogenetic stimulation of identified Schaffer collateral axons with two-photon imaging of postsynaptic calcium signals and follow the fate of individual synapses for 7 d after LTD induction. Optogenetic stimulation of CA3 pyramidal cells at 1 Hz led to strong and reliable depression of postsynaptic calcium transients in CA1. NMDA receptor activation was necessary for successful induction of LTD. We found that, in the days following LTD, many depressed synapses and their "neighbors" were eliminated from the hippocampal circuit. The average lifetime of synapses on nonstimulated dendritic branches of the same neurons remained unaffected. Persistence of individual depressed synapses was highly correlated with reliability of synaptic transmission, but not with spine size or the amplitude of spine calcium transients. Our data suggest that LTD initially leads to homogeneous depression of synaptic function, followed by selective removal of unreliable synapses and recovery of function in the persistent fraction.long-term plasticity | transmitter release | dendritic spines | calcium imaging | channelrhodopsin L ong-lasting modifications of synaptic transmission are thought to underlie learning and information storage in the brain. Intact synaptic plasticity seems to be a precondition for memory formation, and disturbing long-term depression (LTD) or longterm potentiation (LTP) strongly interferes with learning (1-6). Hippocampal field potential recordings have been used to demonstrate that LTD and LTP can be stable for weeks in vivo, at least at the level of large synaptic populations (7-9). It is less clear, however, whether individual synapses can maintain their strength at a specific level over the time scales of memory. Commonly used recording techniques to assess synaptic plasticity (e.g., whole-cell recordings, field recordings, or imaging of Ca 2+ -sensitive dyes) are too short-lived (10-12) or lack single-synapse resolution (7-9). Therefore, it is not known whether the strength of an individual synapse drifts over time, or how specific activity patterns affect the long-term stability of a synapse.In vivo imaging experiments have shown that dendritic spines in mammalian cortex constantly change their morphology and sometimes completely disappear or form de novo (13-15). Life expectancy and turnover of spines is affected by experience and behavioral paradigms, suggesting a regulated, activity-dependent process controlling spine lifetime (16)(17)(18)(19). Could LTP and LTD form the missing link between neuronal activity and lasting structural changes? Indeed, induction of LTP at individual excitatory synapses in vitro leads to increased spine head size (12) and insertion of postsynaptic scaffolding proteins (20) and glutamate receptors (21). Potentiation of in...

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“…It has been shown that ATP released by astrocytes and activating P2Y receptors located at neighbouring nerve terminals caused hLTD; P2Y receptor occupation may depress glutamate release under these conditions [310]. Selective stimulation of astrocytes expressing channel rhodopsin-2, a lightgated cation channel permeable to Ca 2+ , resulted in LTD of synapses on neighbouring neurons.…”

Section: Interplay Between Purinergic and Glutamatergic Systems In Thmentioning

confidence: 99%

Modulation of excitatory neurotransmission by neuronal/glial signalling molecules: interplay between purinergic and glutamatergic systems

Köles

Kató

Hanuska

et al. 2015

Purinergic Signalling

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Glutamate is the main excitatory neurotransmitter of the central nervous system (CNS), released both from neurons and glial cells. Acting via ionotropic (NMDA, AMPA, kainate) and metabotropic glutamate receptors, it is critically involved in essential regulatory functions. Disturbances of glutamatergic neurotransmission can be detected in cognitive and neurodegenerative disorders. This paper summarizes the present knowledge on the modulation of glutamate-mediated responses in the CNS. Emphasis will be put on NMDA receptor channels, which are essential executive and integrative elements of the glutamatergic system. This receptor is crucial for proper functioning of neuronal circuits; its hypofunction or overactivation can result in neuronal disturbances and neurotoxicity. Somewhat surprisingly, NMDA receptors are not widely targeted by pharmacotherapy in clinics; their robust activation or inhibition seems to be desirable only in exceptional cases. However, their fine-tuning might provide a promising manipulation to optimize the activity of the glutamatergic system and to restore proper CNS function. This orchestration utilizes several neuromodulators. Besides the classical ones such as dopamine, novel candidates emerged in the last two decades. The purinergic system is a promising possibility to optimize the activity of the glutamatergic system. It exerts not only direct and indirect influences on NMDA receptors but, by modulating glutamatergic transmission, also plays an important role in glia-neuron communication. These purinergic functions will be illustrated mostly by depicting the modulatory role of the purinergic system on glutamatergic transmission in the prefrontal cortex, a CNS area important for attention, memory and learning.

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Heterosynaptic long‐term depression mediated by ATP released from astrocytes

Cited by 128 publications

References 57 publications

Astrocytes regulate heterogeneity of presynaptic strengths in hippocampal networks

Astrocytes regulate heterogeneity of presynaptic strengths in hippocampal networks

Long-term depression triggers the selective elimination of weakly integrated synapses

Modulation of excitatory neurotransmission by neuronal/glial signalling molecules: interplay between purinergic and glutamatergic systems

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