Post-Inhibitory Rebound Spikes in Rat Medial Entorhinal Layer II/III Principal Cells: In-Vivo, In-Vitro, and Computational Modeling Characterization

MICHELE FERRANTE, CHRISTOPHER F SHAY, YUSUKE TSUNO, G WILLIAM CHAPMAN, MICHAEL E HASSELMO

Abstract:

Medial Entorhinal Cortex Layer-II stellate cells (mEC-LII-SCs) primarily interact via inhibitory
interneurons. This suggests the presence of alternative mechanisms other than excitatory synaptic
inputs for triggering action potentials (APs) in stellate cells during spatial navigation. Our
intracellular recordings show that the hyperpolarization-activated cation current (Ih) allows PostInhibitory-Rebound-Spikes (PIRS) in mEC-LII-SCs. In-vivo, strong Inhibitory-Post-SynapticPotentials (IPSPs) immediately preceded most APs shortening their delay and enhancing
excitability. In-vitro experiments showed that inhibition initiated spikes more effectively than
excitation and that more dorsal mEC-LII-SCs produced faster and more synchronous spikes. In
contrast, PIRS in Layer-II/III pyramidal cells (PCs) were harder to evoke, voltage-independent,
and slower in dorsal mEC. In computational simulations, mEC-LII-SCs morphology and
Ih
homeostatically regulated the dorso-ventral (DV) differences in PIRS timing and most dendrites
generated PIRS with a narrow range of stimulus amplitudes. These results suggest inhibitory
inputs could mediate the emergence of grid cell firing in a neuronal network