Plasticity manifolds: Conjunctive changes in multiple ion channels mediate activity-dependent plasticity in hippocampal granule cells

The dentate gyrus (DG) was the first brain region to provide insights about synaptic and intrinsic plasticity. However, the assessment of intrinsic plasticity in DG has been surprisingly limited. We employed whole-cell patch-clamp recordings to explore the impact of behaviorally relevant theta-modulated burst firing, in the absence of synaptic stimulation, on intrinsic properties of rat DG granule cells. We found that theta burst firing induced a significant reduction in sub-threshold excitability and temporal summation, accompanied by an unexpectedly contrasting enhancement of action potential firing rate. We show that conjunctive changes in HCN, inward-rectifier potassium and persistent sodium channels mediated this form of plasticity, which was dependent on calcium influx through L-type calcium channels and inositol trisphosphate receptors. Our results unveil the expression of conjunctive plasticity in multiple channels, responding to the same activity pattern, establishing a plasticity manifold that could concomitantly mediate encoding and homeostasis in DG engram cells.