Calcium: Amplitude, Duration, or Location?

Evans, Rebekah C.; Blackwell, Kim T.

doi:10.1086/bblv228n1p75

Cited by 74 publications

(78 citation statements)

References 65 publications

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“…As has been discussed previously (summarized in Evans & Blackwell, ), calcium amplitude alone is not sufficient to predict plasticity direction. Indeed, a single set of amplitude thresholds are not sufficient to account for all the synaptic plasticity results presented here.…”

Section: Discussionmentioning

confidence: 88%

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Calcium dynamics predict direction of synaptic plasticity in striatal spiny projection neurons

Jędrzejewska-Szmek

Damodaran

Dorman

et al. 2016

Eur J of Neuroscience

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The striatum is a major site of learning and memory formation for sensorimotor and cognitive association. One of the mechanisms used by the brain for memory storage is synaptic plasticity – the long lasting, activity-dependent change in synaptic strength. All forms of synaptic plasticity require an elevation in intracellular calcium, and a common hypothesis is that the amplitude and duration of calcium transients can determine the direction of synaptic plasticity. The utility of this hypothesis in the striatum is unclear in part because dopamine is required for striatal plasticity and in part because of the diversity in stimulation protocols. To test whether calcium can predict plasticity direction, we developed a calcium-based plasticity rule using a spiny projection neuron model with sophisticated calcium dynamics including calcium diffusion, buffering, and pump extrusion. We utilize three spike-timing-dependent plasticity (STDP) induction protocols, in which post-synaptic potentials are paired with precisely timed action potentials and the timing of such pairing determines whether potentiation or depression will occur. Results show that despite the variation in calcium dynamics, a single, calcium-based plasticity rule, which explicitly considers duration of calcium elevations, can explain the direction of synaptic weight change for all three STDP protocols. Additional simulations show that the plasticity rule correctly predicts the NMDA receptor dependence of long-term potentiation and the L-type channel dependence of long term depression. By utilizing realistic calcium dynamics, the model reveals mechanisms controlling synaptic plasticity direction, and shows that the dynamics of calcium, not just calcium amplitude, are crucial for synaptic plasticity.

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Section: Discussionmentioning

confidence: 88%

“…A common hypothesis is that the amplitude and duration of calcium transients can determine the direction of synaptic plasticity (reviewed in Evans & Blackwell, ). Indeed, theoretical analysis shows that an amplitude‐based rule, which ignores duration, cannot prevent LTD with long temporal intervals (Rubin et al ., ).…”

Section: Introductionmentioning

confidence: 99%

Calcium dynamics predict direction of synaptic plasticity in striatal spiny projection neurons

Jędrzejewska-Szmek

Damodaran

Dorman

et al. 2016

Eur J of Neuroscience

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“…This is important since first- or second-order kinetics can carry temporal information themselves. For example, a rapid, high and short rise in postsynaptic calcium is required for induction of LTP, whereas a slow, low and long-lasting rise is needed for LTD (Evans and Blackwell, 2015). It is difficult to disambiguate individual roles for the variables of (i) time, (ii) rate of increase and (iii) peak value of calcium, all of which contribute to the instantaneous intracellular concentration of calcium, the ultimate factor responsible for the plasticity-driving function of calcium influx.…”

Section: Temporal Interactions and Feedback In Synaptic Plasticity: Tmentioning

confidence: 99%

Memory Takes Time

Kukushkin

Carew

2017

Neuron

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Summary Memory is an adaptation to particular temporal properties of past events, such as the frequency of occurrence of a stimulus or the coincidence of multiple stimuli. In neurons, this adaptation can be understood in terms of a hierarchical system of molecular and cellular time windows, which collectively retain information from the past. We propose that this system makes various time scales of past experience simultaneously available for future adjustment of behavior. More generally, we propose that the ability to detect and respond to temporally structured information underlies the nervous system’s capacity to encode and store a memory at molecular, cellular, synaptic and circuit levels.

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“…Calcium plays a pivotal role as a second messenger in many neural signaling pathways (Blackwell, 2013, Evans and Blackwell, 2015). Our model evaluated various scenarios regarding Ca 2+ sourcing, Ca 2+ removal, Ca 2+ binding, and time constants of interaction with target molecules.…”

Section: Discussionmentioning

confidence: 99%

Calcium regulation of HCN channels supports persistent activity in a multiscale model of neocortex

et al. 2016

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Neuronal persistent activity has been primarily assessed in terms of electrical mechanisms, without attention to the complex array of molecular events that also control cell excitability. We developed a multiscale neocortical model proceeding from the molecular to the network level to assess the contributions of calcium regulation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in providing additional and complementary support of continuing activation in the network. The network contained 776 compartmental neurons arranged in the cortical layers, connected using synapses containing AMPA/NMDA/GABAA/GABAB receptors. Metabotropic glutamate receptors (mGluR) produced inositol triphosphate (IP3) which caused release of Ca2+ from endoplasmic reticulum (ER) stores, with reuptake by sarco/ER Ca2+-ATP-ase pumps (SERCA), and influence on HCN channels. Stimulus-induced depolarization led to Ca2+ influx via NMDA and voltage-gated Ca2+ channels (VGCCs). After a delay, mGluR activation led to ER Ca2+ release via IP3 receptors. These factors increased HCN channel conductance and produced firing lasting for ~1 minute. The model displayed inter-scale synergies among synaptic weights, excitation/inhibition balance, firing rates, membrane depolarization, calcium levels, regulation of HCN channels, and induction of persistent activity. The interaction between inhibition and Ca2+ at the HCN channel nexus determined a limited range of inhibition strengths for which intracellular Ca2+ could prepare population-specific persistent activity. Interactions between metabotropic and ionotropic inputs to the neuron demonstrated how multiple pathways could contribute in a complementary manner to persistent activity. Such redundancy and complementarity via multiple pathways is a critical feature of biological systems. Mediation of activation at different time scales, and through different pathways, would be expected to protect against disruption, in this case providing stability for persistent activity.

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Calcium: Amplitude, Duration, or Location?

Cited by 74 publications

References 65 publications

Calcium dynamics predict direction of synaptic plasticity in striatal spiny projection neurons

Calcium dynamics predict direction of synaptic plasticity in striatal spiny projection neurons

Memory Takes Time

Calcium regulation of HCN channels supports persistent activity in a multiscale model of neocortex

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