Acetylcholine

A major neuromodulator in the CNS and neurotransmitter at neuromuscular junctions. It is an ester of acetic acid and choline.

## Location

* neuromuscular junctions
	+ nAChR vs. mAChRs
* autonomic nervous system
* CNS
	+ brainstem
		- mesopontine tegmentum area
			* pedunculopontine nucleus
			* laterodrosal tegmental nucleus
	+ basal forebrain
		- nucleus basalis --> mainly M1Rs in neocortex
		- medial septal nucleus --> M1Rs in hippocampus and cortex

## Function

* "Cholinergic activity consistently increases the efficacy of feedforward processing relative to that of local recurrent connections" (paraphrased a little).
* Stimulating nucleus basalis paired with auditory stimuli can cause massive reorganization of primary auditory cortex in adult rat.
* Can gate the induction of LTD in visual cortical slices along with Norepinephrine and mGluR5 receptors.
* M1R agonist can enable LTD in L2/3 visual cortical rat slices. Together with β-Adrenergic receptor agonists can enable standard STDP (with pre before post leading to LTP).
* Musc. Rs have been shown to increase activation of immediate early genes and expression of plasticity-related genes.
* It's proposed that acetylcholine projections play the role of desynchronizing cortical activity to improve signal to noise ratio for salient information.
	+ De-innervation of cholinergic afferents leads to attention deficits.
	+ stimulation of these afferents can lead to reinforced behavior associated with rewarding or aversive stimuli.
	+ It's also been found to be important for switching neuron networks into high-arousal states.
* A paper found that acetylcholine went up in Hippocampus and Frontal Cortex during REM sleep only when it was followed by wakefulness.
* Acetylcholine binding to receptors on astrocytes can lead to an increase in intracellular Calcium.
* Acetylcholine excites Somatostatin-expressing Neurons, increasing their firing rate in V1. This seems to disinhibit pyramidal neuron leading to a desynchronized state in the cortex.

## References

1. ↑ http://www.sciencedirect.com/science/article/pii/S0306452217306607
2. ↑ Cortical map reorganization enabled by nucleus basalis activity

Science, 279 (1998), pp. 1714–1718
3. ↑ Multiple receptors coupled to PLC gate LTD in visual cortex

J. Neurosci., 25 (2005), pp. 11433–11443
4. ↑ http://www.sciencedirect.com/science/article/pii/S0896627307006265
5. ↑ von der Kammer, H. *et al*. Muscarinic acetylcholine receptors activate expression of the EGR gene family of transcription factors. J. Biol. Chem. 273, 14538–14544 (1998).
6. ↑ Teber, I., Kohling, R., Speckmann, E. J., Barnekow, A. & Kremerskothen, J. Muscarinic acetylcholine receptor stimulation induces expression of the activity-regulated cytoskeleton-associated gene (ARC). Brain Res. Mol. Brain Res. 121, 131–136 (2004).
7. ↑ 7.0 7.1 7.2 7.3 http://www.sciencedirect.com/science/article/pii/S2211124716318071
8. ↑ C.B. Saper, P.M. Fuller, N.P. Pedersen, J. Lu, T.E. Scammell

Sleep state switching

Neuron, 68 (2010), pp. 1023–1042
9. ↑ http://journal.frontiersin.org/article/10.3389/fncir.2017.00003/full
10. ↑ http://www.nature.com.resources.library.brandeis.edu/neuro/journal/v18/n6/full/nn.4002.html