Modelo in vitro para el estudio del papel de la unión mesopontina en la generación del sueño de movimientos oculares rápidos y la vigilia

Esteban Pino, Héctor Kunizawa, Jack Yamuy, Michel Borde

Resumen


El estudio de las estrategias neurales para la organización del comportamiento en vertebrados constituye un desafío mayor para la Neurociencia. El avance del conocimiento en este campo depende de manera crítica de la utilización de modelos experimentales adecuados que admitan múltiples niveles de análisis (p;ej: comportamental, circuital, celular, sináptico, molecular) y abordajes multitécnicos. Nos propusimos analizar in vitro una red neural de la unión mesopontina del tronco encefálico críticamente implicada en el control del sueño de movimientos oculares rápidos (S-REM). Pese al cúmulo de evidencia que apoyan el papel desempeñado por esta red en relación al S-REM, los mecanismos celulares y sinápticos que subyacen a este control son poco conocidos y continúan siendo objeto de intensa investigación.Para avanzar en el conocimiento de estos mecanismos, se llevó a cabo la caracterización morfológica y funcional de una rodaja de tronco encefálico de la rata, en la que las estructuras críticas para el control del  S-REM,  i;e;: núcleos tegmentales laterodorsal y pedúnculopontino, y su proyección al núcleo reticular pontis oralis (PnO), están presentes y son operativas. La inclusión del núcleo motor del trigémino en la rodaja permitió detectar cambios de la excitabilidad de las motoneuronas ante manipulaciones farmacológicas del PnO, representativos de los cambios del tono muscular asociados a maniobras similares realizadas in vivo. La utilización de este modelo in vitro de S-REM, permitirá aportar a la dilucidación de las estrategias neurales que operan en niveles intermedios de organización del SN en mamíferos para la generación y regulación de un estado comportamental.


Palabras clave


sueño REM; vigilia, formación reticulada pontina; PnO; núcleo tegmental laterodorsal; núcleo tegmental pedúnculopontino; acetilcolina; glutamato; GABA; atonía; motoneurona

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Referencias


Kandel ER. Cellular basis of behavior: an introduction to behavioral neurobiology. San Francisco: Freeman; 1976.

Getting PA. Emerging principles governing the operation of neural networks. Annu Rev Neurosci. 1989;12:185-204.

Eaton RC, Lee RK, Foreman MB. The Mauthner cell and other identified neurons of the brainstem escape network of fish. Prog Neurobiol. 2001;63:467-85.

Nusbaum MP, Beenhakker MP. A small-systems approach to motor pattern generation. Nature. 2002;417(6886):343-50.

Marder E, Bucher D. Understanding circuit dynamics using the stomatogastric nervous system of lobsters and crabs. Annu Rev Physiol. 2007;69:291-316.

Brown RE, Basheer R, McKenna JT, Strecker RE, McCarley RW. Control of sleep and wakefulness. Physiol Rev. 2012;92:1087-187.

Fraigne JJ, Torontali ZA, Snow MB, Peever JH. REM sleep at its core-circuits, neurotransmitters, and pathophysiology. Front Neurol. 2015;6:123.

Siegel JM. Brainstem mechanisms generating REM sleep. En: Kryger MK, Roth T, Dement WC. Principles and Practice of Sleep Medicine. 3rd edition. Philadelphia: W.B. Saunders; 2000. p. 112-33.

Sastre JP, Sakai K, Jouvet M. Are the gigantocellular tegmental field neurons responsible for paradoxical sleep? Brain Res. 1981;229:147-61.

Sakai K. Executive mechanisms of paradoxical sleep. Arch Ital Biol. 1988;126:239-57.

Webster HH, Jones BE. Neurotoxic lesions of the dorsolateral pontomesencephalic tegmentum-cholinergic cell area in the cat. II. Effects upon sleep-waking states. Brain Res. 1988;458:285-302.

Baghdoyan HA. Location and quantification of muscarinic receptor subtypes in rat pons: implications for REM sleep generation. Am J Physiol. 1997;273:896-904.

Arrigoni E, Chen MC, Fuller PM. The anatomical, cellular and synaptic basis of motor atonia during rapid eye movement sleep. J Physiol. 2016;594(19):5391-414.

Reinoso-Suárez F, Andrés I de, Rodrigo-Angulo ML, Garzón M. Brain structures and mechanisms involved in the generation of REM sleep. Sleep Med Rev. 2001;5:63-77.

McCarley RW, Hobson JA. Discharge patterns of cat pontine brain stem neurons during desynchronized sleep. J Neurophysiol. 1975;38:751-66.

Lu J, Sherman D, Devor M, Saper CB. A putative flip-flop switch for control of REM sleep. Nature 2006;441:589-94

Datta S, Maclean RR. Neurobiological mechanisms for the regulation of mammalian sleep-wake behavior: reinterpretation of historical evidence and inclusion of contemporary cellular and molecular evidence. Neurosci Biobehav Rev. 2007;31:775-824.

Fuller PM, Saper CB, Lu J. The pontine REM switch: past and present. J Physiol. 2007;584:735-741.

McKenna JT, Chen L, McCarley RW. Neuronal models of REM-sleep control: evolving concepts. En: Mallick BN, Pandi-Perumal SR, McCarley RW, Morrison AR. REM sleep: regulation and function. Cambridge: Cambridge University Press; 2011. p. 285-99.

Pace-Schott EF, Hobson JA. The neurobiology of sleep: genetics, cellular physiology and subcortical networks. Nat Rev Neurosci. 2012;3(8):591-605.

Luppi PH, Gervasoni D, Verret L, Goutagn R, Peyron C, Salvert D, et al. Paradoxical (REM) sleep genesis: the switch from an aminergic-cholinergic to a GABAergic-glutamatergic hypothesis. J Physiol., 2006;100(5):271-83.

Luppi PH, Clement O, Sapin E, Peyron C, Gervasoni D, Léger L, et al. Brainstem mechanisms of paradoxical (REM) sleep generation. Pflügers Arch. 2012;463:43-52.

McCarley RW. Mechanisms and models of REM sleep control. Arch Ital Biol. 2004;142:429-67.

McCarley RW. Neurobiology of REM and NREM sleep. Sleep Med. 2007;8:302-30.

Heister DS, Hayar A, Garcia-Rill E. Cholinergic modulation of GABAergic and glutamatergic transmission in the dorsal subcoeruleus: mechanisms for REM sleep control. Sleep. 2009;32:1135-47.

Weng FJ, Williams RH, Hawryluk JM, Lu J, Scammell TE, Saper CB, et al. Carbachol excites sublaterodorsal nucleus neurons projecting to the spinal cord. J Physiol. 2014;592:1601-17.

Yamuy J, Borde M, Chase MH. Modulation of the activity of pontine reticular neurons by nerve growth factor (NGF). Presentación No. 546.5 en: 34th Neuroscience Meeting Planner; 2004 Oct. 23-27; San Diego, CA.

Kunizawa H, Yamuy J, Borde M. Modelo in vitro para el estudio del papel de la unión mesopontina en la generación del sueño de movimientos oculares rápidos. 1º Congreso IBRO/LARC de Neurociencia; 2008, Sept. 1-4; Buzios, Brasil.

Xi MC, Morales FR, Chase MH. Induction of wakefulness and inhibition of active (REM) sleep by GABAergic processes in the nucleus pontis oralis. Arch Ital Biol. 2001;139(1),125-45.

Xi M-C, Morales FR, Chase MH. Interactions between GABAergic and cholinergic processes in the nucleus pontis oralis: neuronal mechanisms controlling active (rapid eye movement) sleep and wakefulness. J Neurosci. 2004;24:10670-8.

Sanford LD, Tang X, Xiao J, Ross RJ, Morrison AR. GABAergic regulation of REM sleep in reticularis pontis oralis and caudalis in rats. J Neurophysiol. 2003;90:938-45.

Aghajanian GK, Rasmussen K. Intracellular studies in the facial nucleus illustrating a simple new method for obtaining viable motoneurons in adult rat brain slices. Synapse. 1989;3:331-8.

Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflügers Arch. 1981;391:85-100.

Greene RW, Haas HL, McCarley RW. A low threshold calcium spike mediates firing pattern alterations in pontine reticular neurons. Science. 1986;234:738-40.

Gerber U, Greene RW, McCarley RW. Repetitive firing properties of medial pontine reticular formation neurones of the rat recorded in vitro. J Physiol. 1989;410:533-60.

Stevens DR, McCarley RW, Greene RW. Serotonin1 and serotonin2 receptors hyperpolarize and depolarize separate populations of medial pontine reticular formation neurons in vitro. Neuroscience. 1992;47:545-53.

Núñez A, De la Roza C, Rodrigo-Angulo ML, Buño W, Reinoso-Suárez F. Electrophysiological properties and cholinergic responses of rat ventral oral pontine reticular neurons in vitro. Brain Res. 1997;754:1-11.

Núñez A, Buño W, Reinoso-Suárez F. Neurotransmitter actions on oral pontine tegmental neurons of the rat: an in vitro study. Brain Res. 1998;804:144-48.

Núñez A, Rodrigo-Angulo ML, De Andrés I, Reinoso-Suárez F. Firing activity and postsynaptic properties of morphologically identified neurons of ventral oral pontine reticular nucleus. Neuroscience. 2002;115:1165-75.

Mobbs P, Becker D, Williamson R, Bate M, Warner A. Techniques for dye injection and cell labelling. En: D. Ogden. Microelectrode techniques. The Plymouth workshop handbook. Cambridge: The Company of Biologists. 1994. p. 361-87

Kita H, Armstrong W. A biotin-containing compound N-(2-aminoethyl) biotinamide for intracellular labeling and neuronal tracing studies: comparison with biocytin. J Neurosci Methods 1991;37:141-50.

Lapper SR, Bolam JP. The anterograde and retrograde transport of neurobiotin in the central nervous system of the rat: comparison with biocytin. J Neurosci Methods. 1991;39:163-74.

Stone TW. Microiontophoresis and Pressure Ejection. En: Smith Ad. IBRO handbook series: methods in the neurosciences, Vol 8. New York: J. Wiley & Sons; 1985.

Reinoso Suárez F. Modulation by the GABA of the ventro-oral-pontine reticular REM sleep-inducing neurons. An R Acad Nac Med. 2007;124:397-411; discussion 411-13.

Monti JM. Serotonin control of sleep-wake behavior. Sleep Med Rev. 2011;15:269-81.

Paxinos G, Watson C. The rat brain in stereotaxic coordinates, 4ª ed. San Diego: Academic Press; 1998.

Rose HJ, Metherate R. Auditory thalamocortical transmission is reliable and temporally precise. J Neurophysiol. 2005;94:2019-30.

Datta S, Siwek DF. Modulation by the GABA of the ventro-oral-pontine reticular REM sleep-inducing neurons Single cell activity patterns of pedunculopontine tegmentum neurons across the sleep wake cycle in the freely moving rats. J Neurosci Res. 2002;70(4):611-21.

Boucetta S, Cissé Y, Mainville L, Morales M, Jones BE. Discharge profiles across the sleep-waking cycle of identified cholinergic, GABAergic, and glutamatergic neurons in the pontomesencephalic tegmentum of the rat. J Neurosci. 2014;34:4708-27.

Greene RW, Carpenter DO. Actions of neurotransmitters on pontine medial reticular formation neurons of the cat. J Neurophysiol. 1985;54:520-31.

Greene RW, Haas HL, Gerber U, McCarley RW. Cholinergic activation of medial pontine reticular formation neurons in vitro. EXS. 1989;57:123-37.

Stevens DR, Birnstiel S, Gerber U, McCarley RW, Greene RW. Nicotinic depolarizations of rat medial pontine reticular formation neurons studied in vitro. Neuroscience. 1993;57:419-24.

Imon H, Ito K, Dauphin L, McCarley RW. Electrical stimulation of the cholinergic laterodorsal tegmental nucleus elicits scopolamine-sensitive excitatory postsynaptic potentials in medial pontine reticular formation neurons. Neuroscience. 1996;74:393-401.

Ito K, Yanagihara M, Imon H, Dauphin L, McCarley RW. Intracellular recordings of pontine medial gigantocellular tegmental field neurons in the naturally sleeping cat: behavioral state-related activity and soma size difference in order of recruitment. Neuroscience. 2002;114:23-37.

Brown RE, Winston S, Basheer R, Thakkar MM, McCarley RW. Electrophysiological characterization of neurons in the dorsolateral pontine rapid-eye-movement sleep induction zone of the rat: intrinsic membrane properties and responses to carbachol and orexins. Neuroscience. 2006;143(3):739-55.

Coulter DA, Huguenard JR, Prince DA.Calcium currents in rat thalamocortical relay neurones: kinetic properties of the transient, low-threshold current. J Physiol. 1989;414:587-604.

Huguenard JR. Low-threshold calcium currents in central nervous system neurons. Ann Rev Physiol. 1996;58(1):329-48.

Perez-Reyes E. Molecular physiology of low voltage activated T-type calcium channels. Physiol Rev. 2003;83(1):117-61.

Adams PR, Galvan M. Voltage-dependent currents of vertebrate neurons and their role in membrane excitability. Adv Neurol. 1986;44:137-70.

McCormick DA, Pape HC. Properties of a hyperpolarization-activated cation current and its role in rhythmic oscillation in thalamic relay neurones. J Physiol. 1990;431:291-318.

He C, Chen F, Li B, Hu Z. Neurophysiology of HCN channels: from cellular functions to multiple regulations. Prog Neurobiol. 2014;112:1-23.

Kayama Y, Ogawa T. Electrophysiology of ascending, possibly cholinergic neurons in the rat laterodorsal tegmental nucleus: comparison with monoamine neurons. Neurosci Lett. 1987;77:277-82.

Steriade M, Datta S, Paré D, Oakson G, Curró Dossi RC. Neuronal activities in brain-stem cholinergic nuclei related to tonic activation processes in thalamocortical systems. J Neurosci. 1990;10:2541-59

Semba K, Fibiger HC. Afferent connections of the laterodorsal and the pedunculopontine tegmental nuclei in the rat: a retro- and antero-grade transport and immunohistochemical study. J Comp Neurol. 1992;323:387-410.

Semba K. Aminergic and cholinergic afferents to REM sleep induction regions of the pontine reticular formation in the rat. J Comp Neurol. 1993;330:543-56.

Iwasaki H, Kani K, Maeda T. Neural connections of the pontine reticular formation, which connects reciprocally with the nucleus prepositus hypoglossi in the rat. Neuroscience. 1999;93:195-208.

Boissard R, Gervasoni D, Schmidt MH, Barbagli B, Fort P, Luppi PH. The rat ponto-medullary network responsible for paradoxical sleep onset and maintenance: a combined microinjection and functional neuroanatomical study. Eur J Neurosci. 2002;16:1959-73.

Madison DV, Lancaster B, Nicoll RA. Voltage clamp analysis of cholinergic action in the hippocampus. J Neurosci. 1987;7:733-41.

Leonard CS, Llinás R. Serotonergic and cholinergic inhibition of mesopontine cholinergic neurons controlling REM sleep: an in vitro electrophysiological study. Neuroscience. 1994;59:309-30.

Sanchez R, Leonard CS. NMDA-receptor-mediated synaptic currents in guinea pig laterodorsal tegmental neurons in vitro. J Neurophysiol. 1996;76:1101-11.

Luebke JI, Greene RW, Semba K, Kamondi A, McCarley RW, Reiner PB. Serotonin hyperpolarizes cholinergic low-threshold burst neurons in the rat laterodorsal tegmental nucleus in vitro. Proc Natl Acad Sci USA. 1992;89:743-47.

Luebke JI, McCarley RW, Greene RW. Inhibitory action of muscarinic agonists on neurons in the rat laterodorsal tegmental nucleus in vitro. J Neurophysiol. 1993;70:2128-35.

Cornwall J, Cooper JD, Phillipson PT. Projections to the rostral reticular thalamic nucleus in the rat. Exp Brain Res. 1990;80(1):157-71.

Coombs JS, Curtis DR, Eccles JC. The interpretation of spike potentials of motoneurones. J Physiol. 1957;139(2):198-231.

Baghdoyan HA, Rodrigo-Angulo ML, McCarley RW, Hobson JA. Site-specific enhancement and suppression of desynchronized sleep signs following cholinergic stimulation of three brainstem regions. Brain Res. 1984;306(1):39-52.

Morales FR, Boxer P, Chase MH. Behavioral state-specific inhibitory postsynaptic potentials impinge on cat lumbar motoneurons during active sleep. Exp Neurol. 1987;98(2):418-35.

Yamuy J, Fung SJ, Xi M, Morales FR, Chase MH. Hypoglossal motoneurons are postsynaptically inhibited during carbachol-induced rapid eye movement sleep. Neuroscience. 1999;94(1),11-15.

Kubin L. Carbachol models of REM sleep: recent developments and new directions. Arch Ital Biol. 2001;139:147-68.

Grace KP, Vanstone LE, Horner RL. Endogenous cholinergic input to the pontine REM sleep generator is not required for REM sleep to occur. J Neurosci. 2014;34:14198-209.

Mallick BN, Singh A, Khanday MA. Activation of inactivation process initiates rapid eye movement sleep. Prog Neurobiol. 2012;97(3):259-76.

Weber F, Dan Y. Circuit-based interrogation of sleep control. Nature. 2016;538(7623):51-59.

Fernández de Sevilla D, Núñez A, Borde M, Malinow R, Buno W. Cholinergic-mediated IP3-receptor activation induces long-lasting synaptic enhancement in CA1 pyramidal neurons. J Neurosci. 2008;28(6),1469-78.

Thiele, A. Muscarinic signaling in the brain. Ann Rev Neurosci. 2013;36:271-94.

Datta S, Hobson JA. Neuronal activity in the caudolateral peribrachial pons: relationship to PGO waves and rapid eye movements. J Neurophysiol. 1994;71:95-109.

Shiromani PJ, Armstrong DM, Bruce G, Hersh LB, Groves PM, Gillin JC. Relation of pontine choline acetyltransferase immunoreactive neurons with cells which increase discharge during REM sleep. Brain Res Bull. 1987;18:447-55.

Wang HL, Morales M. Pedunculopontine and laterodorsal tegmental nuclei contain distinct populations of cholinergic, glutamatergic and GABAergic neurons in the rat. Eur J Neurosci. 2009;29:340-58.

Grace KP, Horner RL Evaluating the evidence surrounding pontine cholinergic involvement in REM sleep generation. Front Neurol. 2015;6:190.

Boissard R, Fort P, Gervasoni D, Barbagli B, Luppi PH. Localization of the GABAergic and non-GABAergic neurons projecting to the sublaterodorsal nucleus and potentially gating paradoxical sleep onset. Eur J Neurosci. 2003;18:1627-39

Andersen P, Silfvenius H, Sundberg SH, Sveen O, Wigström H. Functional characteristics of unmyelinated fibres in the hippocampal cortex. Brain Res. 1978;144:11-18.

Picciotto MR, Higley MJ, Mineur YS. Acetylcholine as a neuromodulator: cholinergic signaling shapes nervous system function and behavior. Neuron. 2012; 76:116-29.

Morales FR, Sampogna S, Rampon C, Luppi PH, Chase MH. Brainstem glycinergic neurons and their activation during active (rapid eye movement) sleep in the cat. Neuroscience. 2006;142(1):37-47.

Sapin E, Lapray D, Bérod A, Goutagny R, Léger L, Ravassard P. et al. Localization of the brainstem GABAergic neurons controlling paradoxical (REM) sleep. PLoS One. 2009;4(1):e4272.

Siegel JM. REM sleep: A biological and psychological paradox. Sleep Med Rev. 2011;15(3):139-42.

Chase MH.Motor control during sleep and wakefulness: clarifying controversies and resolving paradoxes. Sleep Med Rev. 2013;17(4):299-312.

Chase MH, Morales FR. Subthreshold excitatory activity and motoneuron discharge during REM periods of active sleep. Science. 1983;221(4616):1195-98.

Kubin L, Tojima H, Reignier C, Pack AI, Davies RO. Interaction of serotonergic excitatory drive to hypoglossal motoneurons with carbachol-induced, REM sleep-like atonia. Sleep. 1996;19(3):187-95.

Rekling, JC, Funk GD, Bayliss DA, Dong XW, Feldman JL. Synaptic control of motoneuronal excitability. Physiol Rev. 2000;80(2):767-852.

Brooks PL, Peever JH. Identification of the transmitter and receptor mechanisms responsible for REM sleep paralysis. J Neurosci. 2012;32(29):9785-95.

Vinay L, Brocard F, Pflieger JF, Simeoni-Alias J, Clarac F. Perinatal development of lumbar motoneurons and their inputs in the rat. Brain Res Bull. 2000;53(5):635-47.

Xi, MC, Morales FR, Chase MH. A GABAergic pontine reticular system is involved in the control of wakefulness and sleep. Sleep Res Online. 1999;2(2):43-8.




DOI: http://dx.doi.org/10.25184/anfamed2017.4.1.6

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