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What Behaviors Are Associated With Acetylcholine?

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In the central nervous system, ACh is found primarily in interneurons, shown in Figure 11.3 as orange and green cell clusters. A few important long-axon cholinergic pathways have also been identified. Noteworthy is the cholinergic projection from the nucleus basalis of Meynert (in the basal forebrain) to the forebrain neocortex and associated limbic structures

Degeneration of this pathway is one of the pathologies associated with Alzheimer's disease. There is also a projection from the medial septal and diagonal band region to limbic structures (blue). Most subcortical areas are innervated by neurons from the ponto-mesencephalic region.

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Why is acetylcholine so important in the body? It serves a number of critical functions, many of which can be impaired by diseases or drugs that influence the function of this neurotransmitter

Acetylcholine can be found in all motor neurons, where it stimulates muscles to contract. From the movements of the stomach and heart to the blink of an eyelash, all of the body's movements involve the actions of this important neurotransmitter. It is also found in many brain neurons and plays an important role in mental processes such as memory and cognition. Severe depletion of acetylcholine is associated with Alzheimer's disease. Acetylcholine is not only the most common chemical messenger, but it was also the very first neurotransmitter to be identified. It was discovered by Henry Hallett Dale in 1914, and its existence was later confirmed by Otto Loewi. Both individuals were awarded the Nobel Prize in Physiology/Medicine in 1936 for their discovery. Within the autonomic system, acetylcholine controls a number of functions by acting on preganglionic neurons in the ​sympathetic and parasympathetic systems. It is also the neurotransmitter released at all parasympathetic innervated organs, promoting contraction of smooth muscles, dilation of blood vessels, increased body secretions, and a slower heart rate. For example, the brain might send out a signal to move the right arm. The signal is carried by nerve fibers to the neuromuscular junctions. The signal is transmitted across this junction by the acetylcholine neurotransmitter, triggering the desired response in those specific muscles. Acetylcholine also acts at various sites within the central nervous system where it can function as a neurotransmitter and as a neuromodulator. It plays a role in motivation, arousal, attention, learning, and memory, and is also involved in promoting REM sleep.

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Pharmacological data clearly indicate that both muscarinic and nicotinic acetylcholine receptors play a role in encoding of new memories (Radcliffe KA, Fisher JL, 1999)

Localized lesions and antagonist infusions demonstrate the anatomical locus of these cholinergic effects, and computational modeling links the function of cholinergic modulation to specific cellular effects within these regions. Acetylcholine may enhance encoding by increasing the strength of afferent input relative to feedback, by contributing to theta rhythm oscillations, by activating intrinsic mechanisms for persistent spiking, and by increasing the modification of synapses. These effects may enhance different types of encoding in different cortical structures. In particular, the effects in entorhinal and perirhinal cortex and hippocampus may be important for encoding of new episodic memories (Gil Z, Conners BW, 1997). Pharmacological studies in human subjects conclusively demonstrate that blockade of muscarinic cholinergic receptors by drugs such as scopolamine impairs the encoding of new memories, but not the retrieval of previously stored memories, and impairs working memory for some stimuli. Conversely, drugs which activate nicotinic receptors enhance the encoding of new information. This article will discuss how the specific cellular effects of acetylcholine within cortical structures could underlie the role of acetylcholine in encoding of new memories.

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Definitely, the contribution of acetylcholine to psychiatric illnesses remains an area of active research. For example, increased understanding of mechanisms underlying cholinergic modulation of cortical function has provided insight into attentional dysfunction in schizophrenia. Acetylcholine normally enhances cortical sensitivity to external stimuli and decreases corticocortical communication, increasing focused attention

However, increases in ACh signaling can lead to symptoms related to anxiety and depression. For example, while stress-induced ACh release can result in adaptive responses to environmental stimuli, chronic elevations in cholinergic signaling may produce maladaptive behaviors.

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Pang KC, Nocera R. Interactions between 192-IgG saporin and intraseptal cholinergic and GABAergic drugs: role of cholinergic medial septal neurons in spatial working memory. Behav Neurosci. 1999

Giocomo LM, Hasselmo ME. Nicotinic modulation of glutamatergic synaptic transmission in region CA3 of the hippocampus. Eur J Neurosci. 2005

Radcliffe KA, Fisher JL, Gray R, Dani JA. Nicotinic modulation of glutamate and GABA synaptic transmission of hippocampal neurons. Ann N Y Acad Sci. 1999

Gil Z, Conners BW, Amitai Y. Differential regulation of neocortical synapses by neuromodulators and activity. Neuron. 1997

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