Conjunctive changes in two distinct ion channels mediate activity-dependent intrinsic plasticity in rat dentate gyrus granule cells

Abstract

SUMMARY The concomitant roles of synaptic plasticity and neuron-specific intrinsic plasticity as putative cellular substrates of learning and memory are well established. Although the dentate gyrus (DG) was the first brain region to provide us electrophysiological insights about plasticity in synaptic strength and in intrinsic excitability, the assessment of the protocols, mechanisms and implications associated with intrinsic plasticity in DG has been surprisingly limited. In this study, we focused on identifying behaviorally relevant activity patterns that could induce intrinsic plasticity in granule cells (GC) and on mechanistically understanding such plasticity. We employed whole-cell patch-clamp recordings to explore the impact of intracellularly initiated theta-modulated burst firing, in the absence of synaptic stimulation, on neuronal intrinsic properties of rat GCs. We found that theta burst firing induced a significant reduction in sub-threshold excitability and temporal summation, accompanied by an unexpected contrasting enhancement of supra-threshold excitability in GCs. We show that conjunctive changes in HCN and persistent sodium channels mediated this form of plasticity, which was found to be dependent on influx of cytosolic calcium, with L-type calcium channels and intracellular calcium stores contributing to calcium influx. Our results unveil the expression of conjunctive plasticity in multiple channels, responding to the same activity pattern, thereby establishing a plasticity manifold involving strong rules governing concomitant plasticity in different components. We postulate that activity-dependent increase in neuronal firing rate could act as a putative substrate for the emergence of engram cells, and the associated reduction in sub-threshold excitability could concomitantly provide homeostatic balance and specificity to this encoding process.