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Variability in State-Dependent Plasticity of Intrinsic Properties during Cell-Autonomous Self-Regulation of Calcium Homeostasis in Hippocampal Model Neurons(1,2,3).

Srikanth S, Narayanan R - eNeuro (2015)

Bottom Line: Although calcium homeostasis emerged efficaciously across all models in the population, disparate changes in ionic conductances that mediated this emergence resulted in variable plasticity to several intrinsic properties, also manifesting as significant differences in firing responses across models.We found that the conductance values, intrinsic properties, and firing response of neurons exhibited differential robustness to an intervening switch in the type of afferent activity.These results unveil critical dissociations between different forms of homeostasis, and call for a systematic evaluation of the impact of state-dependent switches in afferent activity on neuronal intrinsic properties during neural coding and homeostasis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cellular Neurophysiology Laboratory, Molecular Biophysics Unit, Indian Institute of Science , Bangalore 560 012, India ; Undergraduate program, Indian Institute of Science , Bangalore 560 012, India.

ABSTRACT
How do neurons reconcile the maintenance of calcium homeostasis with perpetual switches in patterns of afferent activity? Here, we assessed state-dependent evolution of calcium homeostasis in a population of hippocampal pyramidal neuron models, through an adaptation of a recent study on stomatogastric ganglion neurons. Calcium homeostasis was set to emerge through cell-autonomous updates to 12 ionic conductances, responding to different types of synaptically driven afferent activity. We first assessed the impact of theta-frequency inputs on the evolution of ionic conductances toward maintenance of calcium homeostasis. Although calcium homeostasis emerged efficaciously across all models in the population, disparate changes in ionic conductances that mediated this emergence resulted in variable plasticity to several intrinsic properties, also manifesting as significant differences in firing responses across models. Assessing the sensitivity of this form of plasticity, we noted that intrinsic neuronal properties and the firing response were sensitive to the target calcium concentration and to the strength and frequency of afferent activity. Next, we studied the evolution of calcium homeostasis when afferent activity was switched, in different temporal sequences, between two behaviorally distinct types of activity: theta-frequency inputs and sharp-wave ripples riding on largely silent periods. We found that the conductance values, intrinsic properties, and firing response of neurons exhibited differential robustness to an intervening switch in the type of afferent activity. These results unveil critical dissociations between different forms of homeostasis, and call for a systematic evaluation of the impact of state-dependent switches in afferent activity on neuronal intrinsic properties during neural coding and homeostasis.

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The target value of internal calcium concentration critically regulated changes in intrinsic response properties during cell-autonomous self-regulation of calcium homeostasis. A, The steady-state voltage response after theta-dependent evolution plotted for three different target calcium levels (black, 100 nm; red, 200 nm; green, 300 nm). B–H, Histograms of the steady-state measurement values (f250, B; VAP, C; Rin, D; /Z/max, E; fR, F; Q, G; ΦL, H) for the 78 valid models, obtained after theta-dependent evolution with different target calcium levels. The dashed lines in B–H represent the lower and upper bounds for the corresponding measurement (in that order) in the GSA model validation procedure (Table 2).
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Figure 4: The target value of internal calcium concentration critically regulated changes in intrinsic response properties during cell-autonomous self-regulation of calcium homeostasis. A, The steady-state voltage response after theta-dependent evolution plotted for three different target calcium levels (black, 100 nm; red, 200 nm; green, 300 nm). B–H, Histograms of the steady-state measurement values (f250, B; VAP, C; Rin, D; /Z/max, E; fR, F; Q, G; ΦL, H) for the 78 valid models, obtained after theta-dependent evolution with different target calcium levels. The dashed lines in B–H represent the lower and upper bounds for the corresponding measurement (in that order) in the GSA model validation procedure (Table 2).

Mentions: What was the impact of changing the target calcium concentration, [Ca2+]tgt (from the default value of 200 nM), on the temporal evolution of conductances and consequent plasticity in intrinsic properties? To address this, we repeated the θ-dependent evolution experiments (Fig. 3) with two other values for [Ca2+]tgt, set at 100 and 300 nm. We observed neuronal firing at steady state (150 s) of θ-dependent evolution and found that the neuronal model fired more action potentials per θ-cycle upon increase in [Ca2+]tgt. However, at a higher target value (300 nM), the neuron entered into depolarization-induced block with the membrane potential hovering at suprathreshold voltage-levels (Fig. 4A). Turning to steady-state values of intrinsic properties after θ-dependent evolution, we noted that variable plasticity in all seven intrinsic measurements was observed across all three values of [Ca2+]tgt, with no qualitative differences observed in measurement variability with different values of [Ca2+]tgt (Fig. 4B–H).


Variability in State-Dependent Plasticity of Intrinsic Properties during Cell-Autonomous Self-Regulation of Calcium Homeostasis in Hippocampal Model Neurons(1,2,3).

Srikanth S, Narayanan R - eNeuro (2015)

The target value of internal calcium concentration critically regulated changes in intrinsic response properties during cell-autonomous self-regulation of calcium homeostasis. A, The steady-state voltage response after theta-dependent evolution plotted for three different target calcium levels (black, 100 nm; red, 200 nm; green, 300 nm). B–H, Histograms of the steady-state measurement values (f250, B; VAP, C; Rin, D; /Z/max, E; fR, F; Q, G; ΦL, H) for the 78 valid models, obtained after theta-dependent evolution with different target calcium levels. The dashed lines in B–H represent the lower and upper bounds for the corresponding measurement (in that order) in the GSA model validation procedure (Table 2).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4596012&req=5

Figure 4: The target value of internal calcium concentration critically regulated changes in intrinsic response properties during cell-autonomous self-regulation of calcium homeostasis. A, The steady-state voltage response after theta-dependent evolution plotted for three different target calcium levels (black, 100 nm; red, 200 nm; green, 300 nm). B–H, Histograms of the steady-state measurement values (f250, B; VAP, C; Rin, D; /Z/max, E; fR, F; Q, G; ΦL, H) for the 78 valid models, obtained after theta-dependent evolution with different target calcium levels. The dashed lines in B–H represent the lower and upper bounds for the corresponding measurement (in that order) in the GSA model validation procedure (Table 2).
Mentions: What was the impact of changing the target calcium concentration, [Ca2+]tgt (from the default value of 200 nM), on the temporal evolution of conductances and consequent plasticity in intrinsic properties? To address this, we repeated the θ-dependent evolution experiments (Fig. 3) with two other values for [Ca2+]tgt, set at 100 and 300 nm. We observed neuronal firing at steady state (150 s) of θ-dependent evolution and found that the neuronal model fired more action potentials per θ-cycle upon increase in [Ca2+]tgt. However, at a higher target value (300 nM), the neuron entered into depolarization-induced block with the membrane potential hovering at suprathreshold voltage-levels (Fig. 4A). Turning to steady-state values of intrinsic properties after θ-dependent evolution, we noted that variable plasticity in all seven intrinsic measurements was observed across all three values of [Ca2+]tgt, with no qualitative differences observed in measurement variability with different values of [Ca2+]tgt (Fig. 4B–H).

Bottom Line: Although calcium homeostasis emerged efficaciously across all models in the population, disparate changes in ionic conductances that mediated this emergence resulted in variable plasticity to several intrinsic properties, also manifesting as significant differences in firing responses across models.We found that the conductance values, intrinsic properties, and firing response of neurons exhibited differential robustness to an intervening switch in the type of afferent activity.These results unveil critical dissociations between different forms of homeostasis, and call for a systematic evaluation of the impact of state-dependent switches in afferent activity on neuronal intrinsic properties during neural coding and homeostasis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cellular Neurophysiology Laboratory, Molecular Biophysics Unit, Indian Institute of Science , Bangalore 560 012, India ; Undergraduate program, Indian Institute of Science , Bangalore 560 012, India.

ABSTRACT
How do neurons reconcile the maintenance of calcium homeostasis with perpetual switches in patterns of afferent activity? Here, we assessed state-dependent evolution of calcium homeostasis in a population of hippocampal pyramidal neuron models, through an adaptation of a recent study on stomatogastric ganglion neurons. Calcium homeostasis was set to emerge through cell-autonomous updates to 12 ionic conductances, responding to different types of synaptically driven afferent activity. We first assessed the impact of theta-frequency inputs on the evolution of ionic conductances toward maintenance of calcium homeostasis. Although calcium homeostasis emerged efficaciously across all models in the population, disparate changes in ionic conductances that mediated this emergence resulted in variable plasticity to several intrinsic properties, also manifesting as significant differences in firing responses across models. Assessing the sensitivity of this form of plasticity, we noted that intrinsic neuronal properties and the firing response were sensitive to the target calcium concentration and to the strength and frequency of afferent activity. Next, we studied the evolution of calcium homeostasis when afferent activity was switched, in different temporal sequences, between two behaviorally distinct types of activity: theta-frequency inputs and sharp-wave ripples riding on largely silent periods. We found that the conductance values, intrinsic properties, and firing response of neurons exhibited differential robustness to an intervening switch in the type of afferent activity. These results unveil critical dissociations between different forms of homeostasis, and call for a systematic evaluation of the impact of state-dependent switches in afferent activity on neuronal intrinsic properties during neural coding and homeostasis.

No MeSH data available.


Related in: MedlinePlus