Single cholinergic mesopontine tegmental neurons project to both the pontine reticular formation and the thalamus in the rat

Microinjections of the cholinergic agonist carbachol into a caudal part of the pontine reticular formation of the rat induce a rapid eye movement sleep-like state. This carbachol-sensitive region of the pontine reticular formation is innervated by cholinergic neurons in the pedunculopontine and laterodorsol tegmental nuclei. The same population of cholinergic neurons also project heavily to the thalamus, where there is good evidence that acetylcholine facilitates sensory transmission and blocks rhythmic thalamocortical activity. The present study was undertaken to examine the degree to which single cholinergic neurons in the mesopontine tegmentum project to both the carbachol-sensitive region of the pontine reticular formation and the thalamus, by combining double fluorescent retrograde tracing and immunofluorescence with a monoclonal antibody to choline acetyltransferase in the rat. The results indicated that a subpopulation (5-21% ipsilaterally) of cholinergic neurons in the mesopontine tegmentum projects to both the thalamus and the carbachol-sensitive site of the pontine reticular formation, and these neurons represented the majority (45-88%) of cholinergic neurons projecting to the pontine reticular formation site. The percentage of cholinergic neurons with dual projections was higher in the pedunculopontine tegmental nucleus (6-27%) than in the laterodorsal tegmental nucleus (4-11%). In addition, mixed with cholinergic neurons in the mesopontine tegmentum, there was a small population of dually projecting neurons that did not appear to be cholinergic. Mesopontine cholinergic neurons with dual projections may simultaneously modulate neuronal activity in the pontine reticular formation and the thalamus, and thereby have the potential of concurrently regulating different aspects of rapid eye movement sleep.

[1]  G. Juhász,et al.  Neuronal Firing in the Pallidal Region: Firing Patterns during Sleep-wakefulness Cycle in Cats , 2022 .

[2]  A. Parent,et al.  Projections of brainstem core cholinergic and non-cholinergic neurons of cat to intralaminar and reticular thalamic nuclei , 1988, Neuroscience.

[3]  P. Shiromani,et al.  Pontine neuronal response to local cholinergic infusion: Relation to REM sleep , 1986, Brain Research.

[4]  C. Saper,et al.  Medullary and spinal efferents of the pedunculopontine tegmental nucleus and adjacent mesopontine tegmentum in the rat , 1988, The Journal of comparative neurology.

[5]  A. Parent,et al.  Cholinergic and non-cholinergic neurons of cat basal forebrain project to reticular and mediodorsal thalamic nuclei , 1987, Brain Research.

[6]  M. Descheˆnes,et al.  The cellular mechanism of thalamic ponto-geniculo-occipital waves , 1989, Neuroscience.

[7]  B. Wainer,et al.  Ascending projections from the pedunculopontine tegmental nucleus and the adjacent mesopontine tegmentum in the rat , 1988, The Journal of comparative neurology.

[8]  David A. McCormick,et al.  Acetylcholine induces burst firing in thalamic reticular neurones by activating a potassium conductance , 1986, Nature.

[9]  G. Buzsáki,et al.  Nucleus basalis and thalamic control of neocortical activity in the freely moving rat , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[10]  H. Fibiger,et al.  Brainstem afferents to the magnocellular basal forebrain studied by axonal transport, immunohistochemistry, and electrophysiology in the rat , 1988, The Journal of comparative neurology.

[11]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[12]  D. McCormick Cholinergic and noradrenergic modulation of thalamocortical processing , 1989, Trends in Neurosciences.

[13]  T. Ogawa,et al.  Cholinergic influence of the laterodorsal tegmental nucleus on neuronal activity in the rat lateral geniculate nucleus. , 1986, Journal of neurophysiology.

[14]  D. McCormick,et al.  Actions of acetylcholine in the guinea‐pig and cat medial and lateral geniculate nuclei, in vitro. , 1987, The Journal of physiology.

[15]  Stanley J. Watson,et al.  The rat brain in stereotaxic coordinates (2nd edn) by George Paxinos and Charles Watson, Academic Press, 1986. £40.00/$80.00 (264 pages) ISBN 012 547 6213 , 1987, Trends in Neurosciences.

[16]  J. Gnadt,et al.  Cholinergic brainstem mechanisms of REM sleep in the rat , 1986, Brain Research.

[17]  A. Levey,et al.  Cholinergic nucleus basalis neurons may influence the cortex via the thalamus , 1987, Neuroscience Letters.

[18]  Barbara E. Jones,et al.  Neurotoxic lesions of the dorsolateral pontomesencephalic tegmentum-cholinergic cell area in the cat. II. Effects upon sleep-waking states , 1988, Brain Research.

[19]  R. McCarley,et al.  Alterations in membrane potential and excitability of cat medial pontine reticular formation neurons during changes in naturally occurring sleep-wake states , 1984, Brain Research.

[20]  H. Fibiger,et al.  Basal forebrain and mesopontine tegmental projections to the reticular thalamic nucleus: an axonal collateralization and immunohistochemical study in the rat , 1989, Brain Research.

[21]  B. Jacobs Brain monoaminergic unit activity in behaving animals , 1987 .

[22]  D. Armstrong,et al.  Cholinergic neurons from the dorsolateral pons project to the medial pons: A WGA-HRP and choline acetyltransferase immunohistochemical study , 1988, Neuroscience Letters.

[23]  R. Llinás,et al.  The functional states of the thalamus and the associated neuronal interplay. , 1988, Physiological reviews.

[24]  David A. McCormick,et al.  Acetylcholine inhibits identified interneurons in the cat lateral geniculate nucleus , 1988, Nature.

[25]  M. Deschenes,et al.  The thalamus as a neuronal oscillator , 1984, Brain Research Reviews.

[26]  J J Quattrochi,et al.  Mapping neuronal inputs to REM sleep induction sites with carbachol-fluorescent microspheres. , 1989, Science.

[27]  S. Foote,et al.  Extrathalamic modulation of cortical function. , 1987, Annual review of neuroscience.

[28]  H. Fibiger,et al.  Organization of central cholinergic systems. , 1989, Progress in brain research.

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

[30]  G. Holstege,et al.  Propriobulbar fibre connections to the trigeminal, facial and hypoglossal motor nuclei. I. An anterograde degeneration study in the cat. , 1977, Brain : a journal of neurology.

[31]  H. Thoenen,et al.  Production of specific antisera and monoclonal antibodies to choline acetyltransferase: characterization and use for identification of cholinergic neurons. , 1982, The EMBO journal.

[32]  B. L. Baxter Induction of both emotional behavior and a novel form of REM sleep by chemical stimulation applied to cat mesencephalon. , 1969, Experimental neurology.

[33]  D. Araujo,et al.  Characterization and quantitative autoradiographic distribution of [3H]acetylcholine muscarinic receptors in mammalian brain. Apparent labelling of an M2-like receptor sub-type , 1989, Neuroscience.

[34]  Robert W. McCarley,et al.  Site-specific enhancement and suppression of desynchronized sleep signs following cholinergic stimulation of three brainstem regions , 1984, Brain Research.

[35]  A. Levey,et al.  The origins of cholinergic and other subcortical afferents to the thalamus in the rat , 1987, The Journal of comparative neurology.

[36]  J. Palacios,et al.  Muscarinic cholinergic receptor subtypes in the rat brain. I. Quantitative autoradiographic studies , 1986, Brain Research.

[37]  R. Vertes Brainstem control of the events of rem sleep , 1984, Progress in Neurobiology.

[38]  L. Butcher,et al.  Cholinergic systems in the rat brain: IV. descending projections of the pontomesencephalic tegmentum , 1989, Brain Research Bulletin.

[39]  R. McCarley,et al.  Cholinergic activation of medial pontine reticular formation neurons in vitro , 1989, Brain Research.

[40]  A. C. Cuello,et al.  Cholinergic projections from the midbrain and pons to the thalamus in the rat, identified by combined retrograde tracing and choline acetyltransferase immunohistochemistry , 1985, Brain Research.

[41]  M. Descheˆnes,et al.  The effects of brainstem peribrachial stimulation on perigeniculate neurons: The blockage of spindle waves , 1989, Neuroscience.

[42]  D. Spencer,et al.  Direct autoradiographic determination of M1 and M2 muscarinic acetylcholine receptor distribution in the rat brain: Relation to cholinergic nuclei and projections , 1986, Brain Research.

[43]  A. Parent,et al.  Projections of cholinergic and non-cholinergic neurons of the brainstem core to relay and associational thalamic nuclei in the cat and macaque monkey , 1988, Neuroscience.

[44]  H. Fibiger,et al.  Cholinergic neurons of the laterodorsal tegmental nucleus: Efferent and afferent connections , 1986, The Journal of comparative neurology.

[45]  R. Szymusiak,et al.  Sleep-related neuronal discharge in the basal forebrain of cats , 1986, Brain Research.

[46]  M. Mitler,et al.  Cataplectic-like behavior in cats after micro-injections of carbachol in pontine reticular formation. , 1974, Brain research.

[47]  R. McCarley,et al.  Cholinergic projections from the laterodorsal and pedunculopontine tegmental nuclei to the pontine gigantocellular tegmental field in the cat , 1988, Brain Research.

[48]  M. Descheˆnes,et al.  The effects of brainstem peribrachial stimulation on neurons of the lateral geniculate nucleus , 1989, Neuroscience.

[49]  J. Winn,et al.  Brain , 1878, The Lancet.

[50]  A. Levey,et al.  Choline acetyltransferase immunoreactivity in the rat thalamus , 1987, The Journal of comparative neurology.

[51]  A. Parent,et al.  Basal forebrain cholinergic and noncholinergic projections to the thalamus and brainstem in cats and monkeys , 1988, The Journal of comparative neurology.

[52]  Barry R. Komisaruk,et al.  Synchrony among rhythmical facial tremor, neocortical ‘ALPHA’ waves, and thalamic non-sensory neuronal bursts in intact awake rats , 1980, Brain Research.

[53]  R. Szymusiak,et al.  Sleep-waking discharge of basal forebrain projection neurons in cats , 1989, Brain Research Bulletin.

[54]  T. Ogawa,et al.  Does the ascending cholinergic projection inhibit or excite neurons in the rat thalamic reticular nucleus? , 1986, Journal of neurophysiology.

[55]  Larry L. Butcher,et al.  Cholinergic systems in the rat brain: III. Projections from the pontomesencephalic tegmentum to the thalamus, tectum, basal ganglia, and basal forebrain , 1986, Brain Research Bulletin.

[56]  P. Reiner Correlational analysis of central noradrenergic neuronal activity and sympathetic tone in behaving cats , 1986, Brain Research.

[57]  J. Palacios,et al.  Muscarinic cholinergic receptor subtypes in the human brain. II. Quantitative autoradiographic studies , 1986, Brain Research.

[58]  B. Jones,et al.  Neurotoxic lesions of the dorsolateral pontomesencephalic tegmentum-cholinergic cell area in the cat. I. Effects upon the cholinergic innervation of the brain , 1988, Brain Research.

[59]  E. Scarnati,et al.  The organization of nucleus tegmenti pedunculopontinus neurons projecting to basal ganglia and thalamus: a retrograde fluorescent double labeling study in the rat , 1987, Neuroscience Letters.