What Is the Pathway Origin and Projections of Acetylcholine?
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The highest OXO concentration significantly inhibited both saline-and MA-primed locomotor activity. In a second set of experiments we characterized the individual contributions of ACh originating in the LDT or pedunculopontine tegmental nucleus (PPT) to MA-induced levels of ACh and DA by administering intra-LDT or PPT OXO and performing in vivo microdialysis in the VTA and NAc. Intra-LDT OXO dose-dependently attenuated the MA-induced increase in ACh within the VTA but had no effect on DA in NAc. Intra-PPT OXO had no effect on ACh or DA levels within the VTA or NAc, respectively. In order to test this, we reversibly inhibited cholinergic neurons in the LDT or PPT via a bilateral microinjection of the muscarinic ACh receptor agonist oxotremorine sesquifumarate (OXO). OXO preferentially binds to M2-type ACh receptors, which are inhibitory autoreceptors that activate a TTX-insensitive hyperpolarization thereby inhibiting neuronal activity and terminal ACh release.
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 consequences of this signaling on behaviors related to drug abuse, attention, food intake, and affect. 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).
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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N. Takata, T. Mishima, C. Hisatsune, T. Nagai, E. Ebisui, K. Mikoshiba, H. Hirase, Astrocyte calcium signaling transforms cholinergic modulation to cortical plasticity in vivo, J. Neurosci., 31 (2011