Central Cholinergic Pathways Neuroanatomy and Some Behavioral Implications

Neurons which synthesize and secrete acetylcholine (ACh) for the purpose of neurotransmission are designated as cholinergic. The pioneering work of Otto Loewi established ACh as a neurotransmitter in the peripheral nervous system (Loewi, 1921). Soon thereafter, the suggestion was made that ACh could also serve a similar purpose in central nervous structures (Dale, 1938). Partial support for this possibility was obtained by pharmacological and physiological investigations which showed that ACh, acetylcholinesterase (AChE), choline acetyltransferase (ChAT), and cholinergic receptor sites were widely distributed throughout the neuraxis and that many central neurons were responsive to ACh (for review see Silver, 1974; Fibiger, 1982; Mesulam et al., 1983b). Observations based on AChE histochemistry provided additional information on the anatomical arrangement of cholinergic pathways in the brain stem, diencephalon, limbic system, and neocortex (Krnjevic and Silver, 1965; Shute and Lewis, 1967). However, uncertainty has always been associated with conclusions based on AChE histochemistry since this enzyme is also present in many noncholinergic neurons. The production of monoclonal and monospecific antibodies to ChAT by several research groups has now provided new and much more reliable information on the distribution of cholinergic neurons and on the organization of their connections (Rossier, 1984; Wainer et al., 1984). Since the presence of ChAT is necessary and probably also sufficient for the synthesis of ACh, the immunohistochemical demonstration of ChAT currently constitutes the most specific anatomical marker for putative cholinergic neurons and their pro¬cesses. Although it is not yet known if all neurons that contain ChAT also secrete ACh, this seems like a reasonable assumption to make, but will ultimately need definitive confirmation through a combination of anatomical and physiological approaches. The contemporary literature on the anatomy of cholinergic neurons is vast and varied. The purpose of this chapter is not to provide a critical review of these developments but to summarize some observations on central cholinergic pathways that my colleagues and I have made in the past 10 years. The papers cited provide additional references to the rich literature on this subject.

[1]  M. Mesulam,et al.  Regional variations in cortical cholinergic innervation: Chemoarchitectonics of acetylcholinesterase-containing fibers in the macaque brain , 1984, Brain Research.

[2]  C. H. Vanderwolf,et al.  Cholinergic activation of the electrocorticogram: Role of the substantia innominata and effects of atropine and quinuclidinyl benzilate , 1984, Brain Research.

[3]  R. Bartus,et al.  Behavioral and neurochemical effects following neurotoxic lesions of a major cholinergic input to the cerebral cortex in the rat , 1983, Pharmacology Biochemistry and Behavior.

[4]  D. Amaral,et al.  An autoradiographic study of the projections of the central nucleus of the monkey amygdala , 1981, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[5]  H. Thoenen,et al.  Cholinergic neurons in the rat cerebral cortex demonstrated by immunohistochemical localization of choline acetyltransferase , 1983, Neuroscience Letters.

[6]  A. Levey,et al.  Cholinergic innervation of cortex by the basal forebrain: Cytochemistry and cortical connections of the septal area, diagonal band nuclei, nucleus basalis (Substantia innominata), and hypothalamus in the rhesus monkey , 1983, The Journal of comparative neurology.

[7]  M. Mesulam,et al.  Three-dimensional representation and cortical projection topography of the nucleus basalis (Ch4) in the macaque: concurrent demonstration of choline acetyltransferase and retrograde transport with a stabilized tetramethylbenzidine method for horseradish peroxidase , 1986, Brain Research.

[8]  C. J. Herrick.  The cerebellum of necturus and other urodele amphibia , 1914 .

[9]  M M Mesulam,et al.  Neural inputs into the nucleus basalis of the substantia innominata (Ch4) in the rhesus monkey. , 1984, Brain : a journal of neurology.

[10]  J. E. Vaughn,et al.  Organization and morphological characteristics of cholonergic neurons: an immunocytochemical study with a monoclonal antibody to choline acetyltransferase , 1983, Brain Research.

[11]  M. Woodruff,et al.  Cholinergic and non-cholinergic septo-hippocampal projections: a double-label horseradish peroxidase-acetylcholinesterase study in the rabbit , 1984, Brain Research.

[12]  M. Mesulam,et al.  Choline acetyltransferase-immunoreactive neurons intrinsic to rodent cortex and distinction from acetylcholinesterase-positive neurons , 1984, Neuroscience.

[13]  H. Fibiger,et al.  The organization and some projections of cholinergic neurons of the mammalian forebrain , 1982, Brain Research Reviews.

[14]  D. Drachman,et al.  Human memory and the cholinergic system. A relationship to aging? , 1974, Archives of neurology.

[15]  C. Shute,et al.  The ascending cholinergic reticular system: neocortical, olfactory and subcortical projections. , 1967, Brain : a journal of neurology.

[16]  J. Phillis,et al.  Acetylcholine-sensitivity of thalamic neurones: its relationship to synaptic transmission. , 1968, British journal of pharmacology and chemotherapy.

[17]  D. Mash,et al.  Cholinergic projections from the parabigeminal nucleus (Ch8) to the superior colliculus in the mouse: a combined analysis of horseradish peroxidase transport and choline acetyltransferase immunohistochemistry , 1986, Brain Research.

[18]  Cholinergic systems in mammalian brain identified with antibodies against choline acetyltransferase , 1984, Neurochemistry International.

[19]  J. Price,et al.  Individual cells in the nucleus basalis-diagonal band complex have restricted axonal projections to the cerebral cortex in the rat , 1983, Brain Research.

[20]  D. Amaral,et al.  The afferent connections of the substantia innominata in the monkey, Macaca fascicularis , 1985, The Journal of comparative neurology.

[21]  M. Mesulam,et al.  Central cholinergic pathways in the rat: An overview based on an alternative nomenclature (Ch1–Ch6) , 1983, Neuroscience.

[22]  L. Butcher,et al.  Cholinergic neurons in the caudate-putamen complex proper are intrinsically organized: A combined evans blue and acetylcholinesterase analysis , 1981, Brain Research Bulletin.

[23]  TATSUYA KANAI,et al.  Mesencephalic Reticular Activating System and Cortical Acetylcholine Output , 1965, Nature.

[24]  C. Saper,et al.  Pedunculopontine tegmental nucleus of the rat: Cytoarchitecture, cytochemistry, and some extrapyramidal connections of the mesopontine tegmentum , 1987, The Journal of comparative neurology.

[25]  J. Rossier.  On the mapping of the cholinergic neurons by immunocytochemistry , 1984, Neurochemistry International.

[26]  M. Herkenham,et al.  Mismatches between neurotransmitter and receptor localizations in brain: observations and implications , 1987, Neuroscience.

[27]  M M Mesulam,et al.  Systematic regional differences in the cholinergic innervation of the primate cerebral cortex: Distribution of enzyme activities and some behavioral implications , 1986, Annals of neurology.

[28]  O MARBURG,et al.  The amygdaloid complex. , 1949, Confinia neurologica.

[29]  T. Arendt,et al.  Neuronal loss in different parts of the nucleus basalis is related to neuritic plaque formation in cortical target areas in alzheimer's disease , 1985, Neuroscience.

[30]  J. Coyle,et al.  Alzheimer disease: Evidence for selective loss of cholinergic neurons in the nucleus basalis , 1981, Annals of neurology.

[31]  A M Graybiel,et al.  The afferent and efferent connections of the feline nucleus tegmenti pedunculopontinus, pars compacta , 1983, The Journal of comparative neurology.

[32]  G. Bonin,et al.  The neocortex of Macaca mulatta , 1947 .

[33]  M. Mesulam,et al.  Choline acetyltransferase-like immunoreactivity in the forebrain of the red-eared pond turtle (Pseudemys scripta elegans) , 1984, Brain Research.

[34]  E. Blass.  Handbook of behavioral neurobiology , 1988 .

[35]  H. Kimura,et al.  The central cholinergic system studied by choline acetyltransferase immunohistochemistry in the cat , 1981, The Journal of comparative neurology.

[36]  R. Hassler,et al.  Habenulo-interpeduncular tract: a possible cholinergic neuron in rat brain. , 1973, Brain research.

[37]  R. Bartus,et al.  The cholinergic hypothesis of geriatric memory dysfunction. , 1982, Science.

[38]  M. Mesulam,et al.  Insula of the old world monkey. Architectonics in the insulo‐orbito‐temporal component of the paralimbic brain , 1982, The Journal of comparative neurology.

[39]  M. Mesulam,et al.  Cholinergic and non-cholinergic septohippocampal pathways , 1985, Neuroscience Letters.

[40]  M. Mishkin.  A memory system in the monkey. , 1982, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[41]  G. Rigdon,et al.  Microinjection of procaine or GABA into the nucleus basalis magnocellularis affects cue-elicited unit responses in the rat frontal cortex , 1984, Experimental Neurology.

[42]  A. Parent,et al.  Morphological characteristics of acetylcholinesterase-containing neurons in the CNS of DFP-treated monkeys Part 2. Diencephalic and medial telencephalic structures , 1977, Journal of the Neurological Sciences.

[43]  W. Cowan,et al.  Some efferent connections of the rostral hypothalamus in the squirrel monkey (Saimiri sciureus) and cat , 1979, The Journal of comparative neurology.

[44]  M. Delong,et al.  Activity of pallidal neurons during movement. , 1971, Journal of neurophysiology.

[45]  M. Mesulam.  Principles of behavioral neurology , 1985 .

[46]  R. Dingledine,et al.  Brain stem stimulation and the acetylcholine‐evoked inhibition of neurones in the feline nucleus reticularis thalami , 1977, The Journal of physiology.

[47]  M. Mesulam,et al.  Acetylcholinesterase-rich projections from the basal forebrain of the rhesus monkey to neocortex , 1976, Brain Research.

[48]  A. Graybiel,et al.  Patterns of muscarinic cholinergic binding in the striatum and their relation to dopamine islands and striosomes , 1985, The Journal of comparative neurology.

[49]  E. Rolls,et al.  The latency of activation of neurones in the lateral hypothalamus and substantia innominata during feeding in the monkey , 1979, Brain Research.

[50]  C. H. Vanderwolf.  The Role of the Cerebral Cortex and Ascending Activating Systems in the Control of Behavior , 1983 .

[51]  D. Janowsky,et al.  A cholinergic-adrenergic hypothesis of mania and depression. , 1972, Lancet.

[52]  P. Davies,et al.  SELECTIVE LOSS OF CENTRAL CHOLINERGIC NEURONS IN ALZHEIMER'S DISEASE , 1976, The Lancet.

[53]  M. Mesulam,et al.  Atlas of cholinergic neurons in the forebrain and upper brainstem of the macaque based on monoclonal choline acetyltransferase immunohistochemistry and acetylcholinesterase histochemistry , 1984, Neuroscience.

[54]  D. Calne.  Parkinsonism. Clinical and neuropharmacologic aspects. , 1978, Postgraduate medicine.

[55]  K. Kubota,et al.  Substantia innominata projection to caudate nucleus in macaque monkeys , 1984, Brain Research.

[56]  W. Nauta,et al.  The isodendritic core of the brain stem , 1966, The Journal of comparative neurology.

[57]  D. Mash,et al.  Loss of M2 muscarine receptors in the cerebral cortex in Alzheimer's disease and experimental cholinergic denervation. , 1985, Science.

[58]  J. Coyle,et al.  Regional heterogeneity of choline acetyltransferase activity in primate neocortex , 1984, Brain Research.

[59]  Ann Silver,et al.  The biology of cholinesterases , 1974 .

[60]  K. Krnjević,et al.  A histochemical study of cholinergic fibres in the cerebral cortex. , 1965, Journal of anatomy.

[61]  M. Mesulam,et al.  Age‐related shrinkage of cortically projecting cholinergic neurons: A selective effect , 1987, Annals of neurology.

[62]  D. McCormick,et al.  Two types of muscarinic response to acetylcholine in mammalian cortical neurons. , 1985, Proceedings of the National Academy of Sciences of the United States of America.