Functional organization and neuromodulation of entorhinal cortex layer II neurons

Morphological and electrophysical properties of layer II neurons from the medial entorhinal cortex were investigated in a rat brain slice preparation to enhance our understanding of the role the entorhinal cortex plays in the gating of afferent stimuli to the hippocampal formation.Morphological characterization revealed that layer II projection neurons fell into two distinct categories. 65% of neurons were identified as the stellate cells described previously. The remaining 35% had, for the most, a pyramidal-like morphology, and were referred to as non-stellates.Electrophysiological characterization revealed that stellates and non-stellates had distinct electroresponsive properties. Notably, stellates, upon d.c. depolarization, generated subthreshold, sinusoidal-like, membrane potential oscillations at a mean frequency of 8.6 Hz and a 1-3 Hz repetitive bursting pattern, referred to as clustering. Non-stellates, when d.c. depolarized, never generated subthreshold oscillations nor spike clusters; instead they readily went into tonic firing.Investigation of the main ionic mechanisms endowing stellates and non-stellates with their differential electroresponsiveness revealed that stellates exclusively possessed a fast, low threshold, Ba$ sp{2+}$-sensitive outward rectifier, which, in interplay with the persistent Na$ sp+$ conductance, generated the membrane potential oscillations.The cholinergic agonist carbachol caused a depolarization in both stellates and non-stellates, associated with no change or a slight increase in apparent input resistance. In stellates, carbachol caused a decrease in the dominant frequency of the subthreshold membrane potential oscillations from 9.2 to 6.3 Hz. In non-stellates, carbachol transformed tonic firing into a slow voltage-dependent bursting discharge.Investigation of the ionic mechanisms of the carbachol-induced depolarization in stellates and non-stellates revealed that it resulted mainly from activation of a Ca$ sp{2+}$ dependent cationic conductance largely carried by Na$ sp+$, mediated predominantly through m1 muscarinic receptor subtype activation.Serotonin, in stellates, caused a variable response consisting of a hyperpolarization and/or depolarization, associated with a decrease in apparent input resistance, while in non-stellates, only the hyperpolarizing response was observed. In stellates, serotonin increased the frequency of subthreshold oscillations from 8.5 to 14.0 Hz. In non-stellates, serotonin did not affect spike-train adaptation nor the slow afterhyperpolarization following the train of spikes while it reduced both in stellates.These results attest to the presence, in layer II of the medial entorhinal cortex, of two parallel information processing channels, both projecting to the hippocampal formation, and differentially modulated by the cholinergic and serotoninergic systems. One of these, the stellate channel, is endowed with robust rhythmic properties whose fundamental frequency can vary widely, depending on the relative tone of these two major neurotransmitter systems