IONIC MECHANISMS FOR THE SUBTHRESHOLD OSCILLATIONS AND DIFFERENTIAL ELECTRORESPONSIVENESS OF MEDIAL ENTORHINAL CORTEX LAYER-II NEURONS

1. Layer II of the medial entorhinal cortex is composed of two electrophysiologically and morphologically distinct types of projection neurons: stellate cells (SCs), which are distinguished by rhythmic subthreshold oscillatory activity, and non-SCs. The ionic mechanisms underlying their differential electroresponsiveness, particularly in the subthreshold range of membrane potentials, were investigated in an ''in vitro'' slice preparation. 2. In both SCs and non-SCs, the apparent membrane input resistance was markedly voltage dependent, respectively decreasing or increasing at hyperpolarized or subthreshold depolarized potential levels. Thus the neurons displayed inward rectification in the hyperpolarizing and depolarizing range. 3. In the depolarizing range, inward rectification was blocked by tetrodotoxin (TTX, 1 muM) in both types of neurons and thus shown to depend on the presence of a persistent low-threshold Na+ conductance (g(Nap)). However, in the presence of TTX, pronounced outward rectification became manifest in the subthreshold depolarizing range of membrane potentials (positive to -60 mV) in the SCs but not in the non-SCs. 4. The rhythmic subthreshold membrane potential oscillations that were present only in the SCs were abolished by TTX and not by Ca2+ conductance block with Cd2+ or Co2+. Subthreshold oscillations thus rely on the activation of voltage-gated Na+, and not Ca2+, conductances. The Ca2+ conductance block also had no effect on the subthreshold outward rectification. 5. Prominent time-dependent inward rectification in the hyperpolarizing range in the SCs persisted after Na+- and Ca2+ conductance block. This rectification was not affected by Ba2+ (1 mM), but was blocked by Cs+ (1-4 mM). Therefore, it is most probably generated by a hyperpolarization-activated cationic current (Q-like current). However, the Q-like current appears to play no major role in the generation of subthreshold rhythmic membrane potential oscillations, because these persisted in the presence of Cs+. 6. On the other hand, in the SCs, the fast, sustained, outward rectification that strongly developed (after Na+ conductance block) at the oscillatory voltage level was not affected by Cs+ but was blocked by Ba2+ (1 mM). Barium was also effective in blocking the subthreshold membrane potential oscillations. 7. In the non-SCs, which do not generate subthreshold rhythmic membrane potential oscillations or manifest subthreshold outward rectification in TTX, Ca2+ conductance block abolished spike repolarization and caused the development of long-lasting Na+-dependent plateau potentials at a high suprathreshold voltage level. At this level, where prominent delayed rectification is present, the Na+ plateaus sustained rhythmic membrane Potential oscillations. In the SCs, Ca2+ conductance block caused only a spike broadening at the base and blocked the fast afterhyperpolarization. 8. The results provide further evidence that the different electroresponsiveness of SCs versus non-SCs rests to a large extent in a different expression of ionic conductances in their respective neuronal membranes. With regard to the distinct rhythmic subthreshold oscillations present only in the SCs, the data suggest that their mechanism of generation relies on the interplay of g(Nap) and a subthreshold outward rectifying K+ conductance.