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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.

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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.


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Across different model neurons, switch in afferent activity between θ oscillations and SWRs triggered variable changes in neuronal intrinsic response properties during cell-autonomous self-regulation of calcium homeostasis. A–G, θ1–SWR–θ2 constitutes the temporal sequence of afferent activity, with notations shown in Figure 9A. Histogram of percentage changes in the seven intrinsic response properties (f250, A; VAP, B; Rin, C; /Z/max, D; fR, E; Q, F; ΦL, G) measured at steady state of evolution with θ-frequency oscillations (after θ1–SWR–θ2), computed with reference to the corresponding base value of the intrinsic property measured at steady state of evolution after θ1. Percentage changes in subthreshold measurements (Rin, /Z/max, fR, Q, ΦL) were computed only for those models that did not fire action potentials in response to the injected stimulus. In addition, models that showed very high percentage changes in ΦL were eliminated. The number of models (n) used for each histogram is mentioned in the respective panel. H–N, Same as A–G, but for a SWR1–theta–SWR2 temporal sequence of afferent activity, with notations shown in Figure 10A.
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Figure 11: Across different model neurons, switch in afferent activity between θ oscillations and SWRs triggered variable changes in neuronal intrinsic response properties during cell-autonomous self-regulation of calcium homeostasis. A–G, θ1–SWR–θ2 constitutes the temporal sequence of afferent activity, with notations shown in Figure 9A. Histogram of percentage changes in the seven intrinsic response properties (f250, A; VAP, B; Rin, C; /Z/max, D; fR, E; Q, F; ΦL, G) measured at steady state of evolution with θ-frequency oscillations (after θ1–SWR–θ2), computed with reference to the corresponding base value of the intrinsic property measured at steady state of evolution after θ1. Percentage changes in subthreshold measurements (Rin, /Z/max, fR, Q, ΦL) were computed only for those models that did not fire action potentials in response to the injected stimulus. In addition, models that showed very high percentage changes in ΦL were eliminated. The number of models (n) used for each histogram is mentioned in the respective panel. H–N, Same as A–G, but for a SWR1–theta–SWR2 temporal sequence of afferent activity, with notations shown in Figure 10A.

Mentions: Finally, we asked how state-dependent evolution of calcium homeostasis altered neuronal intrinsic properties. To do this, we measured seven intrinsic properties (Fig. 1) at steady states of temporal evolution with activity pattern (theta or SWR) with the theta–SWR–theta (Fig. 9) and the SWR–theta–SWR (Fig. 10) sequences. Analysis of the evolution of intrinsic properties with switch in afferent activity revealed several important observations. First, intrinsic properties underwent significant plasticity as a consequence of these switches in types of afferent activity, and the sign and strength of this plasticity varied across different model neurons. Second, in the process of such activity-dependent evolution, neuronal intrinsic properties did not necessarily fall into their established experimental bounds (Figs. 9, 10; Table 2). These results reveal a significant dissociation between functional and calcium homeostasis. Third, when neurons were presented with identical (the initial pattern preceding the switch) activity patterns after an intervening period of switch in activity type, there were models whose intrinsic measurements did not restore to values before the intervening period. However, a significant proportion of neurons were robust to the intervening period of activity switch, where their intrinsic properties were restored when the activity pattern was switched back (Fig. 11). Similar to our observation with conductances, we noted that the percentage of neurons robust (in terms of changes in measurements) to an intervening period of activity switch was lower for the theta–SWR–theta (Fig. 11A–G) compared with the percentage for SWR–theta–SWR sequence (Fig. 11H–N). We also noted that neurons fired significantly higher during the theta periods and lesser during SWR periods, which was partly due to overall reduction in intrinsic excitability of the neurons during SWR period (Figs. 7–11).


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)

Across different model neurons, switch in afferent activity between θ oscillations and SWRs triggered variable changes in neuronal intrinsic response properties during cell-autonomous self-regulation of calcium homeostasis. A–G, θ1–SWR–θ2 constitutes the temporal sequence of afferent activity, with notations shown in Figure 9A. Histogram of percentage changes in the seven intrinsic response properties (f250, A; VAP, B; Rin, C; /Z/max, D; fR, E; Q, F; ΦL, G) measured at steady state of evolution with θ-frequency oscillations (after θ1–SWR–θ2), computed with reference to the corresponding base value of the intrinsic property measured at steady state of evolution after θ1. Percentage changes in subthreshold measurements (Rin, /Z/max, fR, Q, ΦL) were computed only for those models that did not fire action potentials in response to the injected stimulus. In addition, models that showed very high percentage changes in ΦL were eliminated. The number of models (n) used for each histogram is mentioned in the respective panel. H–N, Same as A–G, but for a SWR1–theta–SWR2 temporal sequence of afferent activity, with notations shown in Figure 10A.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 11: Across different model neurons, switch in afferent activity between θ oscillations and SWRs triggered variable changes in neuronal intrinsic response properties during cell-autonomous self-regulation of calcium homeostasis. A–G, θ1–SWR–θ2 constitutes the temporal sequence of afferent activity, with notations shown in Figure 9A. Histogram of percentage changes in the seven intrinsic response properties (f250, A; VAP, B; Rin, C; /Z/max, D; fR, E; Q, F; ΦL, G) measured at steady state of evolution with θ-frequency oscillations (after θ1–SWR–θ2), computed with reference to the corresponding base value of the intrinsic property measured at steady state of evolution after θ1. Percentage changes in subthreshold measurements (Rin, /Z/max, fR, Q, ΦL) were computed only for those models that did not fire action potentials in response to the injected stimulus. In addition, models that showed very high percentage changes in ΦL were eliminated. The number of models (n) used for each histogram is mentioned in the respective panel. H–N, Same as A–G, but for a SWR1–theta–SWR2 temporal sequence of afferent activity, with notations shown in Figure 10A.
Mentions: Finally, we asked how state-dependent evolution of calcium homeostasis altered neuronal intrinsic properties. To do this, we measured seven intrinsic properties (Fig. 1) at steady states of temporal evolution with activity pattern (theta or SWR) with the theta–SWR–theta (Fig. 9) and the SWR–theta–SWR (Fig. 10) sequences. Analysis of the evolution of intrinsic properties with switch in afferent activity revealed several important observations. First, intrinsic properties underwent significant plasticity as a consequence of these switches in types of afferent activity, and the sign and strength of this plasticity varied across different model neurons. Second, in the process of such activity-dependent evolution, neuronal intrinsic properties did not necessarily fall into their established experimental bounds (Figs. 9, 10; Table 2). These results reveal a significant dissociation between functional and calcium homeostasis. Third, when neurons were presented with identical (the initial pattern preceding the switch) activity patterns after an intervening period of switch in activity type, there were models whose intrinsic measurements did not restore to values before the intervening period. However, a significant proportion of neurons were robust to the intervening period of activity switch, where their intrinsic properties were restored when the activity pattern was switched back (Fig. 11). Similar to our observation with conductances, we noted that the percentage of neurons robust (in terms of changes in measurements) to an intervening period of activity switch was lower for the theta–SWR–theta (Fig. 11A–G) compared with the percentage for SWR–theta–SWR sequence (Fig. 11H–N). We also noted that neurons fired significantly higher during the theta periods and lesser during SWR periods, which was partly due to overall reduction in intrinsic excitability of the neurons during SWR period (Figs. 7–11).

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