The Mechanism of Abrupt Transition between Theta and Hyper-Excitable Spiking Activity in Medial Entorhinal Cortex Layer II Stellate Cells

  title={The Mechanism of Abrupt Transition between Theta and Hyper-Excitable Spiking Activity in Medial Entorhinal Cortex Layer II Stellate Cells},
  author={Tilman Kispersky and John A. White and Horacio G. Rotstein},
  journal={PLoS ONE},
Recent studies have shown that stellate cells (SCs) of the medial entorhinal cortex become hyper-excitable in animal models of temporal lobe epilepsy. These studies have also demonstrated the existence of recurrent connections among SCs, reduced levels of recurrent inhibition in epileptic networks as compared to control ones, and comparable levels of recurrent excitation among SCs in both network types. In this work, we investigate the biophysical and dynamic mechanism of generation of the fast… 

Abrupt and gradual transitions between low and hyperexcited firing frequencies in neuronal models with fast synaptic excitation: a comparative study.

This work used modeling, numerical simulations, and dynamical systems tools to investigate the biophysical and dynamic mechanisms that underlie these two identified modes of transition in recurrently connected neurons via AMPA excitation and demonstrates that these two modes of Transition are qualitatively different and can be linked to different intrinsic properties of the participating neurons.

The effects of periodic and non-periodic inputs on the dynamics of a medial entorhinal cortex layer II stellate cell model

Numerical simulations show that conductance-based synaptic inputs reduce the amplitude of SC’s subthreshold oscillations for low enough value of the maximal synaptic conductance value but amplify these oscillations at a higher range.

Constraints on the synchronization of entorhinal cortex stellate cells.

Computational models are used to investigate the relationships between the presumably genetically determined parameters of stellate cells in layer II of the entorhinal cortex and the ability of coupled populations of these cells to synchronize their intrinsic oscillations and find that parameters giving low intrinsic firing frequencies close to those actually observed are strongly advantageous for both synchronization time and metabolic energy consumption.

Neuronal synchrony and the transition to spontaneous seizures


Results showed that the resting membrane potential and the hyperpolarization-activated potassium channel (h-channel) affect the subthreshold-level activities in stellate cells and the persistent sodium channels only play an amplifying role in these neurons.

Firing frequency response to current and conductance periodic inputs in a Ih/INap biophysical neuron model

The firing frequency patterns generated in response to both current and conductance sinusoidal inputs in a biophysical (conductance-based) neuron model that includes two ionic currents are investigated, showing that the nonlinearities present in the model and the time scale separation between voltage and the h-current gating variables play an important role in determining these patterns.

Spiking resonances in models with the same slow resonant and fast amplifying currents but different subthreshold dynamic properties

This paper investigates the spiking resonant properties of conductance-based models that are biophysically equivalent at the subthreshold level, but dynamically different (parabolic- and cubic-like voltage nullclines), and demonstrates that the effective time scales that operate at the Subthreshold regime do not necessarily determine the existence of a preferred spiking response to oscillatory inputs in the same frequency band.



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

The ability of stellate cells to generate theta oscillations in the presence of generic in vivo-like patterns of stimulation is investigated and suggests that subthreshold oscillations may contribute less to in vivo response properties than has been hypothesized.

Properties and role of I(h) in the pacing of subthreshold oscillations in entorhinal cortex layer II neurons.

Results indicated that the interplay between I(NaP) and I(h) can sustain persistent subthreshold oscillations in SCs, which are thought to be instrumental in implementing theta rhythmicity in the entorhinal-hippocampal network.

Synchronization of Strongly Coupled Excitatory Neurons: Relating Network Behavior to Biophysics

This work applies “spike time response” (STR) methods, in which the effects of synaptic perturbations on the timing of subsequent spikes are used to predict how these neurons may synchronize at theta frequencies, to models of layer II stellate cells of the medial entorhinal cortex.

Subthreshold Na+-dependent theta-like rhythmicity in stellate cells of entorhinal cortex layer II

The finding of a subthreshold, voltage-gated, Na+-dependent rhythmic membrane oscillation in mammalian neurons indicates that rhythmicity in heterogeneous neuronal networks may be supported by different sets of intrinsic ionic mechanisms in each of the neuronal elements involved.

Canard Induced Mixed-Mode Oscillations in a Medial Entorhinal Cortex Layer II Stellate Cell Model

It is shown that the mechanism of generation of subthreshold oscillatory phenomenon is intrinsically nonlinear, involving the participation of both components (fast and slow) of a hyperpolarization-activated current in addition to the voltage and a persistent sodium current.

Gamma Oscillation by Synaptic Inhibition in a Hippocampal Interneuronal Network Model

It is demonstrated that large-scale network synchronization requires a critical (minimal) average number of synaptic contacts per cell, which is not sensitive to the network size, and that the GABAA synaptic transmission provides a suitable mechanism for synchronized gamma oscillations in a sparsely connected network of fast-spiking interneurons.

Synchronization in hybrid neuronal networks of the hippocampal formation.

The results imply that excitatory SCs, but not inhibitory O-LM interneurons, are capable of synchronizing in phase via monosynaptic mutual connections of the biologically appropriate polarity.

Recurrent Circuits in Layer II of Medial Entorhinal Cortex in a Model of Temporal Lobe Epilepsy

It is suggested that in this model of temporal lobe epilepsy, reduced recurrent inhibition contributes to layer II stellate cell hyperexcitability and hypersynchrony, but increased recurrent excitation does not.

Hyperexcitability, Interneurons, and Loss of GABAergic Synapses in Entorhinal Cortex in a Model of Temporal Lobe Epilepsy

Stereological evidence of fewer GABAergic interneurons, fewer gephyrin-immunoreactive punctae, and reduced frequency of spontaneous IPSCs and miniature IPSCs confirmed that layer II stellate cell hyperexcitability is attributable, at least in part, to reduced inhibitory synaptic input.

The dynamic structure underlying subthreshold oscillatory activity and the onset of spikes in a model of medial entorhinal cortex stellate cells

It is argued that in the subthreshold interval (STI) the seven-dimensional model can be reduced to a three-dimensional system of equations with well differentiated times scales and a mechanism for generations of STOs is provided using dynamical systems arguments.