Effects of acetylcholine on neuronal properties in entorhinal cortex

Abstract

The entorhinal cortex (EC) receives prominent cholinergic innervation from the medial septum and the vertical limb of the diagonal band of Broca (MSDB). To understand how cholinergic neurotransmission can modulate behavior, research has been directed toward identification of the specific cellular mechanisms in EC that can be modulated through cholinergic activity. This review focuses on intrinsic cellular properties of neurons in EC that may underlie functions such as working memory, spatial processing, and episodic memory. In particular, the study of stellate cells (SCs) in medial entorhinal has resulted in discovery of correlations between physiological properties of these neurons and properties of the unique spatial representation that is demonstrated through unit recordings of neurons in medial entorhinal cortex (mEC) from awake-behaving animals. A separate line of investigation has demonstrated persistent firing behavior among neurons in EC that is enhanced by cholinergic activity and could underlie working memory. There is also evidence that acetylcholine plays a role in modulation of synaptic transmission that could also enhance mnemonic function in EC. Finally, the local circuits of EC demonstrate a variety of interneuron physiology, which is also subject to cholinergic modulation. Together these effects alter the dynamics of EC to underlie the functional role of acetylcholine in memory.

Contribution of Ih to the relative facilitation of synaptic responses induced by carbachol in the entorhinal cortex during repetitive stimulation of the parasubiculum

“…In addition, our data are consistent with the relative facilitation of synaptic responses by carbachol being due in part to closure of I h channels. The relative facilitation induced by CCh was associated with a reduction in hyperpolarization-induced inward rectification characteristic of I h (Dickson et al, 2000b;Heys et al, 2012), and the facilitation effect was mimicked by block of I h using the antagonist ZD7288. Application of ZD7288 blocked the sag in voltage responses to negative current steps and slowed decay of EPSPs, suggesting that a CCh-induced reduction in I h that increases input resistance and enhances temporal summation is a possible mechanism contributing to the relative facilitation effect.…”

Long-lasting changes in neural networks to compensate for altered nicotinic input

“…Most cortical somatostatin interneurons are Martinotti cells that send their axons into superficial layers and form dense axon collateral networks in layer I (75). They are morphologically and physiologically similar to O-LM neurons of the hippocampus (76), which are highly responsive to nicotinic signaling (53, 77). Little is known about the nicotinic responsiveness of cortical somatostatin neurons.…”

Nicotinic regulation of experience-dependent plasticity in visual cortex

“…It is possible that the minor subpopulation of deep layer SST interneurons that express Lypd6 was not well represented in the previous negative reports. Although the detailed characteristics of this minor cortical subpopulation of SST interneurons is yet to be known, interestingly in the hippocampus there is a morphologically and electrophysiologically similar population of SST interneurons found in the oriens-lacunosum moleculare (O-LM) that have high responsiveness to nicotinic signaling and also happen to express Lypd6 (Heys et al, 2012; Demars and Morishita, 2014). Interestingly, hippocampal O-LM SST interneurons (Jia et al, 2010) are known to express α2-containing nAChR with a unique non-desensitizing characteristic that allows continual activation and calcium entry in the presence of nicotine, which mediates nicotine-facilitated LTP induction in these neurons (Jia et al, 2010).…”