Ionic mechanisms for the subthreshold oscillations and differential electroresponsiveness of medial entorhinal cortex layer II neurons

Abstract

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 microM) in both types of neurons and thus shown to depend on the presence of a persistent low-threshold Na+ conductance (gNap). 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.(ABSTRACT TRUNCATED AT 400 WORDS)

A metric for space

“…Preliminary observations suggest that grid scale increases in a step-like manner along the dorsoventral axis of the medial entorhinal cortex , much as predicted by the neural network models, which explicitly or implicitly rely on a discontinuous arrangement of modules with different grid spacing and grid orientation (Fuhs and Touretzky, 2006;McNaughton et al, 2006). The wave interference model, on the other hand, is consistent with the existence of intrinsic membrane potential oscillations in the theta frequency range in medial entorhinal layer II neurons (Alonso and Llinas, 1989;Klink and Alonso, 1993), and the fact that the frequency of these intrinsic oscillations decreases from dorsal to ventral levels of the medial entorhinal cortex Giocomo and Hasselmo, 2008), just like the spatial frequency of grid fields decreases along this same axis (Fyhn et al, 2004;Hafting et al, 2005;Brun et al, 2008). The wave interference models also predict the existence of phase precession in grid cells, as, according to the model, the discharge times are determined also by the faster component of the interference wave, whose frequency exceeds that of the theta rhythm in the field.…”

Artificial Synaptic Conductances Reduce Subthreshold Oscillations and Periodic Firing in Stellate Cells of the Entorhinal Cortex

“…Stellate cells produce subthreshold and perithreshold oscillations in the theta band of frequencies, defined here as 3 to7 Hz, ranging in amplitude from 2 to 6 mV (Alonso and Llinas, 1989;Alonso and Klink, 1993;Klink and Alonso, 1993;Giocomo et al, 2007) (Fig. 1 A).…”

Upregulation of the Voltage-Gated Sodium Channel β2 Subunit in Neuropathic Pain Models: Characterization of Expression in Injured and Non-Injured Primary Sensory Neurons

“…play a major role in the initiation and propagation of action potentials, repetitive firing, and amplification of synaptic potentials, as well as in generating subthreshold membrane potential oscillations (Klink and Alonso, 1993;Franceschetti et al, 1995;Catterall, 2000). Increased expression of the ␤2 subunit after nerve injury may contribute to the altered sodium channel activity that is so characteristic of neuropathic pain.…”