Ion channel correlations emerge from the homeostatic regulation of multiple neuronal properties

Jane Yang (1,2), Steve Prescott (1,2,3)

1. Institute of Biomaterials and Biomedical Engineering, University of Toronto

2. The Hospital for Sick Children

3. Department of Physiology, University of Toronto

Neurons must maintain multiple properties amid internal and external fluctuations. Failure of neuronal homeostasis may contribute to many neurological disorders (e.g. neuropathic pain and epilepsy). Previous work simulating homeostatic plasticity as activity-dependent co-regulation of ion channels showed that the relative rates of regulation explain correlations that emerge between regulated ion channels (O’leary et al. 2015, Neuron 88:1308). But we hypothesized that ion channel correlations also depend on other factors not previously considered, including the need to maintain >1 neuronal property. To investigate this, we implemented a simple model of O’leary’s homeostatic rule to adjust up to five conductances to maintain rheobase alone or rheobase plus another property like ATP per spike. We found that ion channel correlations weakened as N, the number of tunable conductances, was increased whereas correlations strengthened as M, the number of regulated neuronal properties, was increased. Strong correlations were observed when M equals N – 1, even when ion channel combinations yielding the desired solution were found by means other than the homeostatic learning rule. Our results demonstrate that maintaining multiple neuronal properties requires up or downregulation of many ion channels, and that ion channel correlations emerge especially when there is a limited number of tunable ion channels relative to the number of neuronal properties requiring regulation.