Summary diagram illustrating the physiological implications for the calcium-dependent plasticity rule governing changes in the <i>h</i> current, and its interactions with calcium-dependent synaptic plasticity.

<p>(A) In the absence of a homeostatic mechanism, the calcium-dependent synaptic plasticity rule acts as a positive feedback loop. Increase in synaptic weight through LTP leads to further enhancement of synaptic strength given the direct dependence of calcium influx on synaptic strength, and the dependence of synaptic plasticity on the calcium influx. Thus repeated potentiation leads to saturation of synaptic strength. Whereas the diagram depicts the case for LTP, a similar diagram would follow for LTD as well, and synapses would die in the case of repeated depression. This positive feedback loop would thus lead to a loss of firing rate homeostasis (Figs. 2 and 3), saturation/death of synapses (during repeated potentiation/depression respectively) ensuring that synapses do not retain a useful dynamic range (Fig. 5), and a loss in the robustness of information transfer across the neuron under a rate-coding schema (Fig. 6). (B) Under the scenario where the HCN channel conductance (<i>g</i>_h) was updated using CDPR, and was updated in parallel to changes in synaptic strength, change in <i>h</i> current (<i>I</i>_h) alters excitability and temporal summation thereby modulating calcium influx into neurons. This change in calcium influx introduces a metaplastic shift to the synaptic plasticity profile <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055590#pone.0055590-Narayanan1" target="_blank">[13]</a> and forms a negative feedback mechanism that counters the positive feedback associated with the calcium-dependent synaptic plasticity in (A). Thus, HCN channel plasticity through CDPR acts as a homeostatic feedback mechanism ensuring that there is retention of firing rate homeostasis (Figs. 2, 3, and 4), of synapses in a useful dynamic range (Fig. 5), and of the robustness of information transfer across the neuron (Fig. 6).