Synaptic amplification by dendritic spines enhances input cooperativity

Harnett, Mark T.; Makara, Judit K.; Spruston, Nelson; Kath, William L.; Magee, Jeffrey C.

doi:10.1038/nature11554

Cited by 252 publications

(342 citation statements)

References 36 publications

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“…However, besides this biochemical role, spines have also been hypothesized to play an electrical role, altering excitatory postsynaptic potentials (EPSPs) (22)(23)(24)(25)(26)(27)(28)(29)(30). Consistent with this idea, activating spines with two-photon uncaging of glutamate generates potentials whose amplitudes are inversely proportional to the length of the spine neck (31), and these responses are much larger in spines than in adjacent dendritic shafts (32). Also, spine conductances can be activated independently of dendritic ones (33)(34)(35)(36).…”

mentioning

confidence: 48%

Activity-dependent dendritic spine neck changes are correlated with synaptic strength

Araya

Vogels

Yuste

2014

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

187

236

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Most excitatory inputs in the mammalian brain are made on dendritic spines, rather than on dendritic shafts. Spines compartmentalize calcium, and this biochemical isolation can underlie input-specific synaptic plasticity, providing a raison d'etre for spines. However, recent results indicate that the spine can experience a membrane potential different from that in the parent dendrite, as though the spine neck electrically isolated the spine. Here we use two-photon calcium imaging of mouse neocortical pyramidal neurons to analyze the correlation between the morphologies of spines activated under minimal synaptic stimulation and the excitatory postsynaptic potentials they generate. We find that excitatory postsynaptic potential amplitudes are inversely correlated with spine neck lengths. Furthermore, a spike timing-dependent plasticity protocol, in which two-photon glutamate uncaging over a spine is paired with postsynaptic spikes, produces rapid shrinkage of the spine neck and concomitant increases in the amplitude of the evoked spine potentials. Using numerical simulations, we explore the parameter regimes for the spine neck resistance and synaptic conductance changes necessary to explain our observations. Our data, directly correlating synaptic and morphological plasticity, imply that long-necked spines have small or negligible somatic voltage contributions, but that, upon synaptic stimulation paired with postsynaptic activity, they can shorten their necks and increase synaptic efficacy, thus changing the input/output gain of pyramidal neurons.STDP | neocortex | basal dendrites D endritic spines are found in neurons throughout the central nervous system (1), and in pyramidal neurons receive the majority of excitatory inputs, whereas dendritic shafts are normally devoid of glutamatergic synapses (2-7). These facts suggest that spines are likely to play an essential role in neural circuits (1), although it is still unclear exactly what this role is (8, 9). Because of their peculiar morphology, hypotheses regarding the specific function of spines have focused on their role in biochemical compartmentalization, whereby a small spine head, where the excitatory synapse is located, is separated from the parent dendrite by a thin neck, isolating the spine cytoplasm from the dendrite (10). Indeed, spines are diffusionally restricted from dendrites (11-13) and compartmentalize calcium after synaptic stimulation (14-16). This local biochemistry and the high calcium accumulations observed following temporal pairing of neuronal input and output (14,17,18) are thought to be responsible for input-specific synaptic plasticity (19-21). However, besides this biochemical role, spines have also been hypothesized to play an electrical role, altering excitatory postsynaptic potentials (EPSPs) (22-30). Consistent with this idea, activating spines with two-photon uncaging of glutamate generates potentials whose amplitudes are inversely proportional to the length of the spine neck (31), and these responses are much larger in spines than...

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mentioning

confidence: 48%

Activity-dependent dendritic spine neck changes are correlated with synaptic strength

Araya

Vogels

Yuste

2014

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

187

236

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“…Previous studies based on EM 25 or diffusion measurements 9 reported a range of 1 to 400 MΩ for R neck , whereas a recent study based on Ca 2+ imaging estimated R neck to be relatively large (500 MΩ) and to very little across spines, which suggests that morphology does not a play a major 16 role 44 . Encompassing these values, our measurements revealed a broad distribution, indicating that, at any given time, half of all spines have R neck values larger than 56 MΩ, with 5% having resistances larger than 500 MΩ.…”

Section: Reliable Estimates Of Spine Neck Resistancementioning

confidence: 86%

“…Spines with shorter and wider necks will 18 be able to sustain stronger synaptic currents, because the driving force will be effectively maintained even during large or repeated synaptic conductance changes. In this way, the observed neck changes may functionally disinhibit the synapse, which could contribute to synaptic weight changes during LTP 44,49 . Taken together, our findings challenge the widespread notion that spines primarily shape biochemical rather than electrical signaling at synapses.…”

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confidence: 99%

Spine neck plasticity regulates compartmentalization of synapses

et al. 2014

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Dendritic spines have been proposed to transform synaptic signals through chemical and electrical compartmentalization. However, the quantitative contribution of spine morphology to synapse compartmentalization and its dynamic regulation are still poorly understood.We used time-lapse superresolution STED imaging in combination with FRAP measurements, 2-photon glutamate uncaging, electrophysiology and simulations to investigate the dynamic link between nanoscale anatomy and compartmentalization in live spines of CA1 neurons in mouse brain slices.We report a diversity of spine morphologies that argues against common categorization schemes, and establish a close link between compartmentalization and spine morphology, where spine neck width is the most critical morphological parameter. We demonstrate that spine necks are plastic structures that become wider and shorter after LTP. These morphological changes are predicted to lead to a substantial drop in spine head EPSP, while leaving overall biochemical compartmentalization preserved. 3 Dendritic spines form the postsynaptic component of most excitatory synapses, whose plasticity is essential for brain development and higher brain functions 1,2 . In addition to the molecular composition of the synapse, the morphology of spines is thought to be critical for synaptic function, as spine head size correlates with synaptic strength 3,4 and undergoes changes during synaptic plasticity [5][6][7][8] . Even so, our understanding of how spine structure shapes synapse function remains fragmented.It is well established that spines compartmentalize biochemical signals 9 . By contrast, the quantitative contribution of spine morphology to compartmentalization is still unknown, and only moderate correlations between spine neck length or head volume and chemical diffusion have been reported [9][10][11] . It is an open question to what extent biochemical compartmentalization is determined primarily by spine geometry or intracellular factors such as organelles or protein assemblies.Concerning electrical compartmentalization, it is not clear how electrical signals are transformed by the spine neck 9,[12][13][14] . This is an important question because synaptic strength may be adjusted through structural changes in spine necks, which has been a long-standing hypothesis 15,16 . An early electron microscopy study reported that the average spine head becomes larger and the neck wider and shorter after the induction of long-term plasticity (LTP) 17 , which was corroborated more recently by work based on 2-photon microscopy 6,18,19 . However, it is not known how these structural changes might affect biochemical and electrical compartmentalization, because 2-photon microscopy does not have sufficient spatial resolution to properly resolve spines and electron microscopy cannot be combined with functional assays. 4 Here, we combined stimulated emission depletion (STED) microscopy, fluorescence recovery after photo-bleaching (FRAP) experiments, 2-photon glutamate uncaging, and patch-clam...

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“…A major finding is that spine heads are not isopotential with the parent dendrite, implying that spine heads are quasiindependent electrical compartments [18]. Importantly, however, the NMDA spike that occurs in the spine head requires both synaptic input to that spine and depolarization from other spines, thus implementing the Hebbian association.…”

Section: (A) Short-term Potentiationmentioning

confidence: 99%

Glutamatergic synapses are structurally and biochemically complex because of multiple plasticity processes: long-term potentiation, long-term depression, short-term potentiation and scaling

Lisman

2017

Phil. Trans. R. Soc. B

136

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Synapses are complex because they perform multiple functions, including at least six mechanistically different forms of plasticity. Here, I comment on recent developments regarding these processes. (i) Short-term potentiation (STP), a Hebbian processthat requires small amounts of synaptic input, appearsto make strong contributions to some forms of working memory. (ii) The rules for long-term potentiation (LTP) induction in CA3 have been clarified: induction does not depend obligatorily on backpropagating sodium spikes but, rather, on dendritic branch-specific N-methyl-D-aspartate (NMDA) spikes. (iii) Late LTP, a process that requires a dopamine signal (and is therefore neoHebbian), is mediated by trans-synaptic growth of the synapse, a growth that occurs about an hour after LTP induction. (iv) LTD processes are complex and include both homosynaptic and heterosynaptic forms. (v) Synaptic scaling produced by changes in activity levels are not primarily cell-autonomous, but rather depend on network activity. (vi) The evidence for distance-dependent scaling along the primary dendrite is firm, and a plausible structural-based mechanism is suggested.Ideas about the mechanisms of synaptic function need to take into consideration newly emerging data about synaptic structure. Recent superresolution studies indicate that glutamatergic synapses are modular (module size 70 -80 nm), as predicted by theoretical work. Modules are trans-synaptic structures and have high concentrations of postsynaptic density-95 (PSD-95) and a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor. These modules function as quasi-independent loci of AMPA-mediated transmission and may be independently modifiable, suggesting a new understanding of quantal transmission.This article is part of the themed issue 'Integrating Hebbian and homeostatic plasticity.'

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Synaptic amplification by dendritic spines enhances input cooperativity

Cited by 252 publications

References 36 publications

Activity-dependent dendritic spine neck changes are correlated with synaptic strength

Activity-dependent dendritic spine neck changes are correlated with synaptic strength

Spine neck plasticity regulates compartmentalization of synapses

Glutamatergic synapses are structurally and biochemically complex because of multiple plasticity processes: long-term potentiation, long-term depression, short-term potentiation and scaling

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