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- Dickson, C. T., et al.
(författare)
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Properties and role of I-h in the pacing of subthreshold oscillations in entorhinal cortex layer II neurons
- 2000
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Ingår i: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 83:5, s. 2562-2579
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Forskningsöversikt (refereegranskat)abstract
- Various subsets of brain neurons express a hyperpolarization-activated inward current (I-h) that has been shown to be instrumental in pacing oscillatory activity at both a single-cell and a network level. A characteristic feature of the stellate cells (SCs) of entorhinal cortex (EC) layer II, those neurons giving rise to the main component of the perforant path input to the hippocampal formation, is their ability to generate persistent, Na+-dependent rhythmic subthreshold membrane potential oscillations, which are thought to be instrumental in implementing theta rhythmicity in the entorhinal-hippocampal network. The SCs also display a robust time-dependent inward rectification in the hyperpolarizing direction that may contribute to the generation of these oscillations. We performed whole cell recordings of SCs in in vitro slices to investigate the specific biophysical and pharmacological properties of the current underlying this inward rectification and to clarify its potential role in the genesis of the subthreshold oscillations. In voltage-clamp conditions, hyperpolarizing voltage steps evoked a slow, noninactivating inward current, which also deactivated slowly on depolarization. This current was identified as I-h because it was resistant to extracellular Ba2+, sensitive to Cs+, completely and selectively abolished by ZD7288, and carried by both Na+ and K+ ions. I-h in the SCs had an activation threshold and reversal potential at approximately -45 and -20 mV, respectively. Its half-activation voltage was -77 mV. Importantly, bath perfusion with ZD7288, but not Ba2+ gradually and completely abolished the subthreshold oscillations, thus directly implicating I-h in their generation. Using experimentally derived biophysical parameters for I-h and the low-threshold persistent Na+ current (I-NaP) present in the SCs, a simplified model of these neurons was constructed and their subthreshold electroresponsiveness simulated. This indicated that the interplay between I-NaP and I-h can sustain persistent subthreshold oscillations in SCs. I-NaP and I-h operate in a push-pull fashion where the delay in the activation/deactivation of I-h gives rise to the oscillatory process.
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| 2. |
- Fransén, Erik, 1962-, et al.
(författare)
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Ionic mechanisms in the generation of subthreshold oscillations and action potential clustering in entorhinal layer II stellate neurons
- 2004
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Ingår i: Hippocampus. - : Wiley. - 1050-9631 .- 1098-1063. ; 14:3, s. 368-384
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Tidskriftsartikel (refereegranskat)abstract
- A multi compartmental biophysical model of entorhinal cortex layer II stellate cells was developed to analyze the ionic basis of physiological properties, such as subthreshold membrane potential oscillations, action potential clustering, and the medium afterhyperpolarization. In particular, the simulation illustrates the interaction of the persistent sodium current (I-NaP) and the hyperpolarization activated inward current (I-h) in the generation of subthreshold membrane potential oscillations. The potential role of I-h in contributing to the medium hyperpolarization (mAHP) and rebound spiking was studied. The role of I-h and the slow calcium-activated potassium current I-K(AHP) in action potential clustering was also studied. Representations of I-h and I-NaP were developed with parameters based on voltage-clamp data from whole-cell patch and single channel recordings of stellate cells (Dickson et A, J Neurophysiol 83:2562-2579, 2000; Magistretti and Alonso, J Gen Physiol 114:491-509, 1999; Magistretti et al., J Physiol 521:629-636, 1999a; J Neurosci 19:7334-7341, 1999b). These currents interacted to generate robust subthreshold membrane potentials with amplitude and frequency corresponding to data observed in the whole cell patch recordings. The model was also able to account for effects of pharmacological manipulations, including blockade of I-h with ZD7288, partial blockade with cesium, and the influence of barium on oscillations. In a model with a wider range of currents, the transition from oscillations to single spiking, to spike clustering, and finally tonic firing could be replicated. In agreement with experiment, blockade of calcium channels in the model strongly reduced clustering. In the voltage interval during which no data are available, the model predicts that the slow component of I-h does not follow the fast component down to very short time constants. The model also predicts that the fast component of I-h is responsible for the involvement in the generation of subthreshold oscillations, and the slow component dominates in the generation of spike clusters.
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