Cerebral cortex, acetylcholine

McCormick, DA and Prince, DA (1986a) Mechanism of action of acetylcholine in the guinea-pig cerebral cortex in vitro. J. Physiol. 375 169-194... 

Basu N, Stamler CJ, Loua KM, Chan HM. 2005a. An interspecies comparison of mercury inhibition on muscarinic acetylcholine receptor binding in the cerebral cortex and cerebellum. Toxicol Appl Pharmacol 205 71-76. 

The pathologic hallmarks of the disease in the brain include neurofibrillary tangles and neuritic plaques made up of various proteins, which result in a shortage of the neurotransmitter acetylcholine. These are primarily located in brain regions involved in learning, memory, and emotional behaviors such as the cerebral cortex, hippocampus, basal forebrain, and amygdala.11... 

Galantamine is a ChE inhibitor, which elevates acetylcholine in the cerebral cortex by slowing the degradation of acetylcholine.37 It also modulates the nicotinic acetylcholine receptors to increase acetylcholine from surviving presynaptic nerve terminals. In addition, it may increase glutamate and serotonin levels. The clinical benefit of action of these additional neurotransmitters is unknown. 

Jasper, ff. ff. Tessier, J. (1971). Acetylcholine liberation from cerebral cortex during paradoxical (REM) sleep. Science 172, 601-2. 

McCormick, D. A. (1993). Actions of acetylcholine in the cerebral cortex and thalamus and implications for function. Prog. Brain. Res. 98, 303-8. 

Celesia, G. G. Jasper, H. H. (1966). Acetylcholine released from cerebral cortex in relation to state of activation. Neurology 16, 1053-64. 

Mitchell, J. F. (1963). The spontaneous and evoked release of acetylcholine from the cerebral cortex. J. Physiol. Lond. 163, 98-116. 

Matsuyama, T., Luiten, P.G.M., Spencer, J. and Strosberg, A.D. (1988) Ultra-structural localisation of immunoreactive sites for muscarinic acetylcholine receptor proteins in the rat cerebral cortex. Neuroscience Research Communications 2, 69-76. 

Several indirect neurochemical effects of methyixanthines contribute to their effects. Micromolar concentrations of caffeine enhance release of acetylcholine (Pedata et al. 1984). However, this effect is biphasic, augmenting release at 50 pM, but decreasing it at 0.5 pM. This effect is also modulatory, affecting stimulated, but not basal, release. Caffeine enhances acetylcholine release in the hippocampus, which is due to adenosine Al receptor subtypes (Carter et al. 1995). Conversely, chronic caffeine reduces the excitatory effect of acetylcholine in the cerebral cortex (Lin and Phillis... 

Opioids dose-dependently reduce the release of acetylcholine in several brain areas, including the hippocampus, striatum, and cerebral cortex... 

Lapchak PA, Araujo DM, Collier B. (1989). Regulation of endogenous acetylcholine release from mammalian brain slices by opiate receptors hippocampus, striatum, and cerebral cortex of guinea-pig and rat. Neuroscience. 31(2) 313-25. 

Jonkman S, Markou A (2006) Blockade of nicotinic acetylcholine or dopamine D 1-fike receptors in the central nucleus of the amygdala or the bed nucleus of the stria terminads does not precipitate nicotine withdrawal in nicotine-dependent rats, Neurosci Lett 400 140-145 Katsura M, Shuto K, Mohri Y, Tsujimura A, Ohkuma S (2001) Withdrawal from nicotine facilitates diazepam binding inhibitor mRNA expression in mouse cerebral cortex. Brain Res Mol Brain Res 97 194-218... 

The nigrostriatal pathway participates in the production of smooth physical motion. It is not the brain area that works to initiate movement, which is in the cerebral cortex (pyramidal tract) it is the region that helps one to have fluid motion (extrapyramidal tract). Although many neurotransmitters are found in this latter system, two neurotransmitters—dopamine and acetylcholine—are predominantly involved in this pathway. The brain normally maintains a relatively stable ratio of dopamine and acetylcholine in the pathway. However, when something happens to upset this ratio, problems arise. 

The available data are consistent with the present thesis that cholinergic inputs to cerebral cortex mediate intradendritic events fundamental to conscious activity as a primary role, and that cholinergic modulation of electrophysiological activity may be secondary, even epiphenomenal. Transduction pathways exist whereby muscarinic receptors (and possibly nicotinic receptors acting presynaptically to inhibit acetylcholine release) may lead to actions on the cytoskeleton directly relevant to consciousness. The thesis presented here describes these pathways and also suggests a possible explanation for the diversity of neuromodulators and metabotropic receptors. Accordingly, qualitative aspects of our consciousness would be finely tuned by a number of neurochemicals, prominent among which is acetylcholine. 

Mechanism of Action Anticholinergic alkaloids that inhibit the action of acetylcholine at postganglionic (muscarinic) receptor sites. Morphine (10% of opium) depresses cerebral cortex, hypothalamus, and medullary centers. Therapeutic Effect Decreases digestive secretions, increases GI muscle tone, reduces G1 force, alters pain perception and emotional response to pain. 

Bianchi C, Siniscalchi A, Beani L 5-HTj, agonists increase and S-HTj agonists decrease acetylcholine efflux from the cerebral cortex of freely moving guinea-pigs. BrJ Pharmacol 101 448-452, 1990... 

Maura G, Andrioli SC, Cavazzani P S-hydroxytryptaminej receptor sites on cholinergic axon terminals of human cerebral cortex mediate inhibition of acetylcholine release. J Neurochem 58 2334-2337, 1992 Mavissakalian M, Turner SM, Michelson L, et al Tricyclic antidepressants in obsessive-compulsive disorder antiobsessional or antidepressant agents 11. Am J Psychiatry 142 572-576, 1985... 

Whitehouse PJ, Price DL, Clark AW, et al Alzheimer disease evidence for selective loss of cholinergic neurons in the nucleus basahs. Ann Neurol 10 122-126, 1981 Whitehouse PJ, Price DL, Struble RG, et al Alzheimer s disease and senile dementia—loss of neurons in the basal forebrain. Science 215 1237-1239, 1982 Whitehouse PJ, Hedreen JC, White CL, et al Basal forebrain neurons in dementia of Parkinson s disease. Ann Neurol 13 243-248, 1983 Whitehouse P, Martino A, Antuono P, et al Nicotinic acetylcholine binding sites in Alzheimer s disease. Brain Res 371 146-151, 1986 Whitehouse PJ, Martino AM, Marcus KA, et al Reductions in acetylcholine and nicotine binding in several degenerative diseases. Arch Neurol 45 722-724, 1988 Whitton PS, Sama GS, O Connell MT The effect of the novel antidepressant tianeptine on the concentration of 5-hydroxytryptamine in rat hippocampal diasylates in vivo. Neuropharmacology 39 1-4, 1991 Whitworth P, Kendall DA Lithium selectively inhibits muscarinic receptor-stimulated inositol tetrakisphosphate accumulation in mouse cerebral cortex slices. J Neurochem 51 258-265, 1988... 

Acetylcholine neuromodulatory system. The neurons that synthesize acetylcholine (molecular formula in box) are located in the pontine brainstem and basal forebrain. The brainstem nuclei (called Ch.5 and 6 in Mesulam s nomenclature) project locally and forward into the thalamus, subthalamus, basal forebrain, and limbic system. The basal forebrain nuclei (Ch.1-4) project to the cerebral cortex and limbic system. Compare with figure 2.1 to identify structures shown. In this and the following three drawings, the very extensive and complex projections to the cerebral cortex are not shown. 

Fig. 1. Occurrence of H3 receptors inhibiting release of acetylcholine, of amino acid and monoamine neurotransmitters in the mammalian CNS in vitro. The schematic drawing represents a midsagittal section of the human brain three areas with a more lateral position are shown by broken line (substantia nigra and part of the hippocampus and of the striatum). For each of the six regions of the CNS (subregions given in brackets), in which H3 heteroreceptors have been identified, the neurotransmitter(s) and the species are indicated. The superscripts refer to the numbers of the papers as listed under References. Own unpublished data suggest that an H3 receptor-mediated inhibition of noradrenaline release also occurs in the human cerebral cortex and hippocampus and in the guinea-pig cerebral cortex. Note that a presynaptic location has not been verified for each of the H3 heteroreceptors or has been even excluded (for details, see Table 1). Abbreviations ACh, acetylcholine DA, dopamine GABA, y-aminobutyric acid Glu, glutamate 5-HT, 5-hydroxytryptamine, serotonin NA, noradrenaline...

High densities of H3 receptors were found in ACh-rich areas such as the cerebral cortex [40]. Furthermore, two different laboratories reported that H3 receptors are involved in the inhibitory effects of histamine on potassium-evoked release of [3H]-acetylcholine (ACh) [53, 54]. However, H3 receptor activation failed to inhibit [3H]-ACh release from rat cortical synaptosomes [54]. Since, as noted above, prudence must always be exerted in in-vivo extrapolation of in-vitro observations, we investigated the effect of histamine on the release of ACh from the cortex of freely moving rats and characterized the underlying mechanisms [55-58]. 

Acetylcholine Cerebral cortex (many areas) basal ganglia limbic and thalamic regions spinal interneurons Excitation... 

Acetylcholine is the neurotransmitter found in many areas of the brain as well as in the periphery (skeletal neuromuscular junction, some autonomic synapses). In the brain, acetylcholine is abundant in the cerebral cortex, and seems to play a critical role in cognition and memory.22 32 Neurons originating in the large pyramidal cells of the motor cortex and many neurons originating in the basal ganglia also secrete acetylcholine from their terminal axons. In general, acetylcholine synapses in the CNS are excitatory in nature. 

Volpicelli LA, Levey AL Muscarinic acetylcholine receptor subtypes in cerebral cortex and hippocampus. Prog Brain Res. 2004 145 59-66. 

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