PT  - JOURNAL ARTICLE
AU  - Sunandha Srikanth
AU  - Rishikesh Narayanan
TI  - Variability in state-dependent plasticity of intrinsic properties during cell-autonomous self-regulation of calcium homeostasis in hippocampal model neurons
AID  - 10.1523/ENEURO.0053-15.2015
DP  - 2015 Aug 11
TA  - eneuro
PG  - ENEURO.0053-15.2015
4099  - http://www.eneuro.org/content/early/2015/08/11/ENEURO.0053-15.2015.short
4100  - http://www.eneuro.org/content/early/2015/08/11/ENEURO.0053-15.2015.full
AB  - 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 towards 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.Significance Statement: A growing body of theoretical and experimental evidence points to neuronal maintenance of calcium homeostasis. The maintenance of such constancy in the face of perpetual switches in behaviorally-driven afferent activity is a paradox, and has not been quantitatively assessed. We assessed cell-autonomous calcium homeostasis in a population of hippocampal model neurons subjected to switches in afferent activity. We found that neuronal conductances and intrinsic properties could undergo variable and significant plasticity towards maintenance of calcium homeostasis through a regime of such behavioral state-dependent changes. Our results also reveal that the maintenance of calcium homeostasis does not necessarily translate to the emergence of individual channelostasis or of functional homeostasis (including firing rate), thereby establishing critical dissociations between different forms of homeostasis.