Diversity and Excitability of Deep Layer Entorhinal Cortical Neurons in a 2 Model of Temporal Lobe Epilepsy

32 The entorhinal cortex (ERC) is critically implicated in temporal lobe epileptogenesis – 33 the most common type of adult-epilepsy. Previous studies have suggested that epileptiform 34 discharges likely initiate in seizure-sensitive deep-layers (V-VI) of the medial entorhinal area 35 (MEA) and propagate into seizure-resistant superficial-layers (II-III) and hippocampus, 36 establishing a lamina-specific distinction between activities of deepversus superficial-layer 37 neurons and their seizure susceptibilities. While layer II stellate cells in MEA have been shown 38 to be hyperexcitable and hypersynchronous in patients and animal models of temporal lobe 39 epilepsy (TLE), the fate of neurons in the deep layers under epileptic conditions and their overall 40 contribution to epileptogenicity of this region has remained unclear. We used whole-cell 41 recordings from slices of the ERC in normal and pilocarpine-treated epileptic rats to characterize 42 the electrophysiological properties of neurons in this region and directly assess changes in their 43 excitatory and inhibitory synaptic drive under epileptic conditions. We found a surprising 44 heterogeneity with at least three major types and two sub-types of functionally-distinct excitatory 45 neurons. However, contrary to expectation, none of the major neuron-types characterized showed 46 any significant changes in their excitability, barring loss of excitatory and inhibitory inputs in a 47 subtype of neuron whose dendrite extended into layer III where neurons are preferentially lost 48 during TLE. We confirmed hyperexcitability of layer II neurons in the same slices, suggesting 49 minimal influence of deep-layer input on superficial-layer neuron excitability under epileptic 50 conditions. These data show that deep layers of ERC contain a more diverse population of 51 excitatory neurons than previously envisaged that appear to belie their seizure-sensitive 52 reputation. 53