Ventral medial entorhinal cortical stellate neuron model: the role of T-type Ca2+ and persistent Na+ (Topczewska et al., accepted)


Dorsal and ventral medial entorhinal cortex (mEC) regions have distinct neural network firing patterns to differentially support functions such as spatial memory. Correspondingly, mEC layer II stellate neuron action potential frequencies vary across the dorsal-ventral axis, with dorsal neurons exhibiting lower firing rates than ventral neurons. This has been partly attributed to higher densities of inhibitory conductances in dorsal compared to ventral neurons. We asked whether additional conductances might also impact this dorsal-ventral gradient in spike firing. We report that T-type Ca 2+ current amplitudes increased three-fold along the dorsal-ventral axis in mEC layer II stellate neurons. Twice as much Ca V 3.2 mRNA was also detected in ventral mEC compared with dorsal mEC. Unusually, as T-type Ca 2+ currents are only transiently active, long depolarizing stimuli applied to ventral, and not dorsal, stellate neurons triggered these currents to cause a sustained rise in membrane voltage and spike firing. This effect was due to T-type Ca 2+ currents acting in concert with persistent Na + currents. T-type Ca 2+ currents themselves prolonged excitatory post-synaptic potentials (EPSPs) to enhance the summation of EPSP trains and augment EPSP-spike coupling in ventral neurons. In contrast, T-type Ca 2+ currents had no effect on dorsal EPSP spike- coupling. These findings indicate that by preferentially regulating ventral neuron spike firing and synaptic potential integration, T-type Ca 2+ currents critically influence the dorsal-ventral gradient in mEC stellate neuron excitability and associated circuit activity.

Region(s) or Organism(s): Entorhinal cortex

Cell Type(s): Entorhinal cortex stellate cell

Currents: I Calcium; I K; I h; I Na,p; I Na,t

Model Concept(s): Action Potentials

Simulation Environment: NEURON

Implementer(s): Giacalone, Elisabetta [elisabetta.giacalone at pa.ibf.cnr.it]; Migliore, Michele [Michele.Migliore at Yale.edu]

References:

Topczewska A et al. (accepted). T-type Ca 2+ and persistent Na + currents synergistically elevate ventral, not dorsal, entorhinal cortical stellate cell excitability Cell Reports.


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