Cholinergic receptor activation supports persistent firing in layer III neurons in the medial entorhinal cortex

Abstract

Medial temporal lobe (MTL) areas are crucial for memory tasks such as spatial working memory and temporal association memory, which require an active maintenance of memory for a short period of time (a few hundred milliseconds to tens of seconds). Recent work has shown that the projection from layer III neurons in the medial entorhinal cortex (MEC) to hippocampal region CA1, the temporoammonic (TA) pathway, might be specially important for these memory tasks. In addition, lesions to the entorhinal cortex disrupt persistent firing in CA1 which is believed to support active maintenance of memory. Injection of cholinergic antagonists and group I mGlu receptor antagonists to the MEC impairs spatial working memory and temporal association memory. Consistent with this, we have shown that group I mGlu receptor activation supports persistent firing in principal cells of the MEC layer III in vitro (Yoshida et al. [39]). However, it still remains unknown whether cholinergic receptor activation also supports persistent firing in MEC layer III neurons. In this paper, we tested this in MEC layer III cells using both ruptured and perforated whole-cell recordings in vitro. We report that the majority of cells we recorded from in MEC layer III show persistent firing during perfusion of the cholinergic agonist carbachol (2–10μM). In addition, repeated stimulation gradually suppressed persistent firing. We further discuss the possible role of persistent firing in memory function in general.