What Is the Pathway Origin and Projections of Acetylcholine?
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ACh is also the neurotransmitter at the adrenal medulla and serves as the neurotransmitter at all the parasympathetic innervated organs. ACh is also the neurotransmitter at the sweat glands, and at the piloerector muscle of the sympathetic ANS. In the central nervous system, ACh is found primarily in interneurons, 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.
The diverse effects of acetylcholine depend on site of release, receptor subtypes, and 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. The definition of a neuromodulator is flexible, but has evolved to describe any kind of neurotransmission that is not directly excitatory (mediated through ionotropic glutamate receptors) or inhibitory (mediated through ionotropic gamma-aminobutyric acid [GABA] receptors) (Ito and Schuman, 2008; Siggins, 1979). Neuromodulation can be thought of as a change in the state of a neuron or group of neurons that alters its response to subsequent stimulation. A number of models have been proposed to explain the actions of ACh in the central nervous system (CNS). For example, ACh has been suggested to be critical for the response to uncertainty, such that an increase in cholinergic tone predicts the unreliability of predictive cues in a known context and improves the signal-to-noise ratio in a learning environment (Yu and Dayan, 2005).
Once this information is available, it would be possible to design medical approaches that can treat highly specific aspects of neurodegenerative disorders leaving all other functions intact. For example, different strategies could be taken to treat the motor symptoms of PD without carrying a cognitive decline and vice versa.
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