Choline‐mediated modulation of hippocampal sharp wave–ripple complexes in vitro

Abstract

The cholinergic system is critically involved in the modulation of cognitive functions, including learning and memory. Acetylcholine acts through muscarinic (mAChRs) and nicotinic receptors (nAChRs), which are both abundantly expressed in the hippocampus. Previous evidence indicates that choline, the precursor and degradation product of Acetylcholine, can itself activate nAChRs and thereby affects intrinsic and synaptic neuronal functions. Here, we asked whether the cellular actions of choline directly affect hippocampal network activity. Using mouse hippocampal slices we found that choline efficiently suppresses spontaneously occurring sharp wave-ripple complexes (SPW-R) and can induce gamma oscillations. In addition, choline reduces synaptic transmission between hippocampal subfields CA3 and CA1. Surprisingly, these effects are mediated by activation of both mAChRs and a7-containing nAChRs. Most nicotinic effects became only apparent after local, fast application of choline, indicating rapid desensitization kinetics of nAChRs. Effects were still present following block of choline uptake and are, therefore, likely because of direct actions of choline at the respective receptors. Together, choline turns out to be a potent regulator of patterned network activity within the hippocampus. These actions may be of importance for understanding state transitions in normal and pathologically altered neuronal networks.

Downstream effects of hippocampal sharp wave ripple oscillations on medial entorhinal cortex layer V neurons in vitro

“…Mean ripple energy was 0.36 ± 0.03 µV*ms and leading frequency of ripples 270 ± 7 Hz ( n = 17). These values are similar to our previous data (Fischer et al, ). SPW‐R in CA1 were regularly followed by negative field potential deflections in the mEC, starting at ∼5–10 ms after the peak of the SPW‐R in CA1.…”

No evidence for role of extracellular choline-acetyltransferase in generation of gamma oscillations in rat hippocampal slices in vitro

“…We also tried to elevate extracellular choline levels by combining HC-3 with acetyl-CoA, again without any effect. We did not apply choline extracellularly as a recent study (Fischer et al, 2014) indicated direct activation of nicotinic and muscarinic receptors which would confound our conclusion.…”

Muscarinic cholinergic receptors modulate inhibitory synaptic rhythms in hippocampus and neocortex

“…Muscarinic acetylcholine receptors (mAChRs) are G-protein coupled receptors of the Class A, rhodopsin-like family, with ACh being the main endogenous agonist (the ACh precursor, choline, reportedly induces γ activity in an atropine-sensitive way at 2–5 mM, Fischer et al, 2014). mAChRs are widely distributed throughout the central nervous system.…”