Calmodulin as a direct detector of Ca2+ signals

Faas, Guido C.; Raghavachari, Sridhar; Lisman, John; Módy, István

doi:10.1038/nn.2746

Cited by 173 publications

(212 citation statements)

References 30 publications

Supporting

Mentioning

201

Contrasting

Order By: Relevance

“…For LTP, we consider that the STDP window is defined by an exponential curve that dictates the instantaneous amount of Ca 2ϩ /calmodulin that will be formed at the time of the postsynaptic spike. In a recent work by Faas et al (2011), the authors have shown that the binding of calmodulin with calcium takes place over a very short timescale, in accordance with our phenomenological description of this process as an instantaneous rise of the corresponding variable at the time of postsynaptic spikes. This variable will be labeled ␦w LTP .…”

Section: Biophysical Correlates Of the Mstdp Modelsupporting

confidence: 80%

Stable Learning in Stochastic Network States

et al. 2012

View full text Add to dashboard Cite

The mammalian cerebral cortex is characterized in vivo by irregular spontaneous activity, but how this ongoing dynamics affects signal processing and learning remains unknown. The associative plasticity rules demonstrated in vitro, mostly in silent networks, are based on the detection of correlations between presynaptic and postsynaptic activity and hence are sensitive to spontaneous activity and spurious correlations. Therefore, they cannot operate in realistic network states. Here, we present a new class of spike-timing-dependent plasticity learning rules with local floating plasticity thresholds, the slow dynamics of which account for metaplasticity. This novel algorithm is shown to both correctly predict homeostasis in synaptic weights and solve the problem of asymptotic stable learning in noisy states. It is shown to naturally encompass many other known types of learning rule, unifying them into a single coherent framework. The mixed presynaptic and postsynaptic dependency of the floating plasticity threshold is justified by a cascade of known molecular pathways, which leads to experimentally testable predictions.

show abstract

Section: Biophysical Correlates Of the Mstdp Modelsupporting

confidence: 80%

Stable Learning in Stochastic Network States

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Following Ca 2+ entry in response to a graded guidance cue, the pathway begins with the rapid binding of Ca 2+ to CaM to form a Ca 2+ / CaM complex [75]. This activates CaN, PKA, and CaMKII at differing levels on each side of the growth cone, depending on the intracellular Ca 2+ concentration.…”

Section: Downstream Effects Of Calciummentioning

confidence: 99%

Calcium signaling in axon guidance

Sutherland

Pujic

Goodhill

2014

Trends in Neurosciences

View full text Add to dashboard Cite

“…With regard to biochemical signaling cascades, tiny ∼fA Ca 2+ fluxes, generally believed not to partake in local signaling, could produce ∼μM Ca 2+ signals sufficient to signal locally to molecules like CaM or CaMKII (34). Nanodomain boosting may similarly play a role in the contraction of ventricular myocytes, where controversy exists regarding whether activation of ryanodine receptors can be triggered by the opening of a single Ca V channel [high-fidelity scenario supported by early experimental work (35)(36)(37)(38)], or if the simultaneous opening of ∼10 channels is necessary [as suggested by recent models that take account of the small ∼fA flux through a single Ca V channel at the +50 mV ventricular plateau potential (39)(40)(41)].…”

Section: Significancementioning

confidence: 99%

Ca ²⁺ channel nanodomains boost local Ca ²⁺ amplitude

Tadross

Tsien

Yue

2013

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

View full text Add to dashboard Cite

Local Ca 2+ signals through voltage-gated Ca 2+ channels (Ca V s) drive synaptic transmission, neural plasticity, and cardiac contraction. Despite the importance of these events, the fundamental relationship between flux through a single Ca V channel and the Ca 2+ signaling concentration within nanometers of its pore has resisted empirical determination, owing to limitations in the spatial resolution and specificity of fluorescence-based Ca 2+ measurements. Here, we exploited Ca 2+ -dependent inactivation of Ca V channels as a nanometer-range Ca 2+ indicator specific to active channels. We observed an unexpected and dramatic boost in nanodomain Ca 2+ amplitude, ten-fold higher than predicted on theoretical grounds. Our results uncover a striking feature of Ca V nanodomains, as diffusion-restricted environments that amplify small Ca 2+ fluxes into enormous local Ca 2+ concentrations. This Ca 2+ tuning by the physical composition of the nanodomain may represent an energy-efficient means of local amplification that maximizes information signaling capacity, while minimizing global Ca 2+ load.L ocal Ca 2+ signals increase the information capacity of signaling within a cell, by enabling short-range signals to operate independently of Ca 2+ events elsewhere throughout the cell (1, 2). These local Ca 2+ signals are the conduit that drives diverse activity-dependent events, such as synaptic transmission (3), neural plasticity (4-6), and cardiac excitation-contraction coupling (7). However, with regard to the Ca 2+ amplitude within nanometers of individual Ca 2+ channels, our knowledge is based predominantly on diffusion theory, which predicts ∼100 μM Ca 2+ signals per picoampere flux at a distance of ∼10 nm from the pore (8-11). Although often quoted, this theory has been difficult to verify experimentally because diffusible Ca 2+ indicators report space-averaged [Ca 2+ ], and thus lack the spatial resolution needed for selective nanodomain reporting. Two recent efforts to overcome this limitation used voltage-gated Ca 2+ channel (Ca V )-tethered fluorescent Ca 2+ indicators to isolate nanodomain signals (12, 13), but were met with unexpected difficulties: Ca V -tethered indicators were unresponsive in the presence of high concentrations of intracellular 1,2-bis(oaminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), a Ca 2+ buffer that preserves Ca 2+ elevations within tens of nanometers of active channels but eliminates it elsewhere (8-10). A lack of response under these conditions would arise if the majority of tethered channels were silent, raising the concern that fluorescence changes observed under milder Ca 2+ buffering (12, 13) may represent the response of indicators tethered to silent channels, which nonetheless eavesdrop on Ca 2+ from active channels nearby. To overcome this fundamental limitation, we used a reverse strategy, whereby Ca 2+ /calmodulin-dependent inactivation (CDI) of channels themselves serves as a nanometer-range indicator of [Ca 2+ ]; a sensitive ionic readout that is unaffected by the pres...

show abstract

Calmodulin as a direct detector of Ca2+ signals

Cited by 173 publications

References 30 publications

Stable Learning in Stochastic Network States

Stable Learning in Stochastic Network States

Calcium signaling in axon guidance

Ca ²⁺ channel nanodomains boost local Ca ²⁺ amplitude

Contact Info

Product

Resources

About

Calmodulin as a direct detector of Ca2+ signals

Cited by 173 publications

References 30 publications

Stable Learning in Stochastic Network States

Stable Learning in Stochastic Network States

Calcium signaling in axon guidance

Ca 2+ channel nanodomains boost local Ca 2+ amplitude

Contact Info

Product

Resources

About

Ca ²⁺ channel nanodomains boost local Ca ²⁺ amplitude