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Is Acetylcholine Excitatory or Inhibitory?

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There are many different kinds of neurotransmitters, and new ones are still being discovered! Over the years, the very idea of what makes something a neurotransmitter has changed and broadened. Because the definition has expanded, some recently discovered neurotransmitters may be viewed as "nontraditional” or “unconventional” (relative to older definitions).

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In our nervous system, the nerve impulse is transfers through neuron, the neuron accept signal from other neuron, integrate the information and then transfer the signal to other cells. Neurons communicate with each other at a specialized junction called synapse. Synapse is a structure that enables the neuron to pass electrical or chemical signal to another neuron or other cells like muscle cell. Synapse is a tiny gap or cleft that can be found between the presynaptic membrane that send information and postsynaptic membrane that receive the information. There are different types of synapses such as axodendritic, axosomatic, axoaxonal and dendrodendritic. Basically, these synapses can be classified into electrical and chemical synapses. Electrical synapse transfers the current through an intercellular channel, the gap junction. The structure of gap junction allows passive transfer of the current whereby the action potential is generated due to the fluctuations in postsynaptic potential. The chemical synapse involves the release of neurotransmitter from the presynaptic membrane to postsynaptic cell as the space between the pre- and post-synaptic neurons is much bigger than that for electrical synapse. The transfer of synapse is recognized as one way conduction in which the synapse impulse only pass through the presynaptic membrane toward the postsynaptic membrane and it will never happen in the reverse direction as the receptor of neurotransmitter can only be found on the postsynaptic membrane. Unlike the other synapses, non-channel synapses comprise of membrane-bound enzymes instead of channel to be the neuroreceptor. When the neurotransmitters bind to the receptor, a series of chemical reaction will be triggered inside the cell. These synapses are usually involved in slow and long-lasting responses. Neuromuscular junctions are the synapses the found between motor neurons and muscle cells connecting the nervous system to muscular system.

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Acetylcholine in the brain alters neuronal excitability, influences synaptic transmission, induces synaptic plasticity and coordinates the firing of groups of neurons. As a result, it changes the state of neuronal networks throughout the brain and modifies their response to internal and external inputs: the classical role of a neuromodulator. Here we identify actions of cholinergic signaling on cellular and synaptic properties of neurons in several brain areas and discuss the consequences of this signaling on behaviors related to drug abuse, attention, food intake, and affect. The diverse effects of acetylcholine depend on the site of release, the receptor subtypes, and the target neuronal population, however, a common theme is that acetylcholine potentiates behaviors that are adaptive to environmental stimuli and decreases responses to ongoing stimuli that do not require immediate action. The ability of acetylcholine to coordinate the response of neuronal networks in many brain areas makes cholinergic modulation an essential mechanism underlying complex behaviors.Acetylcholine (ACh) is a fast-acting, point-to-point neurotransmitter at the neuromuscular junction and in the autonomic ganglia; however, there are fewer demonstrations of similar actions in the brain (Changeux, 2010). Instead, central cholinergic neurotransmission predominantly changes neuronal excitability, alters presynaptic release of neurotransmitters, and coordinates the firing of groups of neurons (Kawai et al., 2007).

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Ultimately, acetylcholine, the first neurotransmitter discovered, was originally described as "vagus stuff" by Otto Loewi because of its ability to mimic the electrical stimulation of the vagus nerve. It is now known to be a neurotransmitter at all autonomic ganglia, at many autonomically innervated organs, at the neuromuscular junction, and at many synapses in the CNS.

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Allosteric receptors: from electric organ to cognition. Changeux JP, Annu Rev Pharmacol Toxicol. 2010; 50():1-38.

Nicotinic control of axon excitability regulates thalamocortical transmission. Kawai H, Lazar R, Metherate R Nat Neurosci. 2007 Sep; 10(9):1168-75.

A disinhibitory microcircuit for associative fear learning in the auditory cortex. Letzkus JJ, Wolff SB, Meyer EM, Tovote P, Courtin J, Herry C, Lüthi A Nature. 2011 Dec 7; 480(7377):331-5.

The role of acetylcholine in learning and memory. Hasselmo ME Curr Opin Neurobiol. 2006 Dec; 16(6):710-5.

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