Reticular activating system

1. Reticular Actvating System Susanth

2. RETICULAR FORMATION Extensive fields of intermingled neurones and nerve fibres in brainstem Ascending and descending components that are partly crossed and uncrossed Highly organized and differentiated, consisting of distinct populations of neurons with specific functions

3. Subserve somatic and visceral functions Receives a summary of much of the sensory information that enters the spinal cord and brain stem ↓ important in influencing the arousal level of an organism Contains interneurons responsible for generating spinal reflexes and simple motor patterns RETICULAR FORMATION

4. RAS Several areas traditionally included are Midbrain Reticular Formation Mesencephalic Nucleus Thalamic  Intralaminar nucleus ( centromedian nucleus) Dorsal Hypothalamus Tegmentum Basal forebrain structures

5. Anatomical subdivisions of RAS Median nuclei Medial nuclei Lateral nuclei

6. MEDIAN COLUMN OF RETICULAR NUCLEI extends throughout the medulla, pons and midbrain bilateral, vertical sheets, blended in the midline and occupying the paramedian zones Collectively called the nuclei of the raphe , or raphe nuclei

7. Serotoninergic and are grouped into nine clusters, B1-9 Medulla Raphe pallidus nucleus and raphe obscurus nucleus Pons Raphe magnus nucleus (B3 neurones ) Pontine raphe nucleus (B5 neurons) Central superior raphe nucleus (B6 and B8 ) Midbrain Dorsal ( rostral ) raphe nucleus ( B7) MEDIAN COLUMN OF RETICULAR NUCLEI

8. Medial Column Of Reticular Nuclei Mostly orientated in the transverse plane Upper medulla Nucleus reticularis gigantocellularis of olszewski and baxter Pons Pontine gigantocellular ( magnocellular ) nucleus Caudal and oral pontine tegmental reticular nuclei Midbrain Cuneiform nucleus and subcuneiform nucleus

9. Lateral Column Of Reticular Nuclei Ventrolateral reticular area Lateral pontine tegmental area Parvocellular reticular area

10. Ventrolateral reticular area Rostrally - Lateral Paragigantocellular Nucleus Caudally - Nucleus Retroambiguus Contains Noradrenergic cell groups A1, A2, A4-A7 (A3 is absent in primates) Adrenergic cell group C1 Lateral Column Of Reticular Nuclei

11. Lateral pontine tegmental reticular grey matter Medial and lateral parabrachial nuclei Ventral kölliker -fuse nucleus - pneumotaxic centre. Locus coeruleus (noradrenergic cell group A6) Area subcoeruleus (Noradrenergic cell group A7) Cholinergic group ch5 in the pedunculopontine tegmental nucleus Two micturition centres - dorsomedial and ventrolateral parts Lateral Column Of Reticular Nuclei

12. Connections of RF Afferent connections Efferent connections

13. Afferents to RF Mainly on medullary reticular formation Spinal cord Collaterals from second order neurons of sensory cranial nuclei Cerebral cortex Cerebellar nuclei

14. Spinal cord Spinoreticular fibres Caudal half of nucleus reticularis gigantocellularis Collaterals of spinothalamic fibres Lateral reticular nucleus → cerebellum Afferents to RF

15. Collateral fibres from auditory, vestibular, trigeminal, visceral ( solitarius ) Parvicellular reticular nucleus Retinotectal and tectoreticular fibres – visual impulses Medial forebrain bundle - olfactory impulses Primary sensory fibres do not terminate on RF (medial leminiscus ) Afferents to RF

16. Cerebral cortex From sensorimotor areas – crossed and uncrossed Nucleus reticularis pontis oralis and caudalis , nucleus reticularis gigantocellularis Afferents to RF

17. Cerebellum Ends on paramedian nuclei Fastigeal nucleus via uncinate fasiculus Dentate nucleus via crossed descending division of superior cerebellar peduncle Afferents to RF

18. Functional Division Magnocellular zone: Large cells restricted to medial two-thirds of reticular formation Parvocellular zone: Small cells found in lateral regions

19. Functional Division Magnocellular zone: Long ascending and descending axons Modulate the actions of neurons involved in movement and posture, pain, autonomic functions, and arousal Parvocellular zone: close to the motor nuclei of the cranial nerves coordinate reflexes and simple stereotyped behaviors mediated by the cranial nerves

20. Parvocellular Reticular Formation Extends from the region lateral to the hypoglossal and ambiguus nuclei through the area surrounding the facial nucleus up to and adjacent to the trigeminal motor nucleus Involved with the coordination of orofacial motor responses Chewing - neurons adjacent to the trigeminal motor nucleus Lip movements - neurons near the facial motor nucleus Movements of the tongue - neurons near the hypoglossal nucleus

21. RF surrounding the facial motor nucleus Organizing emotional facial expressions Descending input is bilateral and facial expressions can be triggered by either hemisphere Pontine paramedian reticular formation Controls ipsilateral horizontal eye movements and majority of fibres to MLF Lateral to the oculomotor nucleus Coordinate vertical eye movements as well as the convergence Parvocellular Reticular Formation

22. Magnocellular Zone Long ascending/descending pathways: Terminate in: Hypothalamus. Midline and intralaminar thalamic nuclei. Segments of spinal cord. Long ascending fibers from: Lower pons and medulla.

23. Ascending Reticular Activating System - ARAS Receives fibers from the sensory pathways via long ascending spinal tracts. Alertness, maintenance of attention and wakefulness. Emotional reactions, important in learning processes .

24. Ascending arousal system (ARAS) Monoaminergic cell groups in the brain stem Ascending cholinergic inputs from the pedunculopontine and laterodorsal tegmental nuclei Junction of the midbrain and diencephalon Activates and modulates thalamic relay nuclei as well as intralaminar and related nuclei Extensive diffuse cortical projections Lateral hypothalamic area hypothalamic and basal forebrain cell groups

25. ARAS Main function is to modify and potentiate thalamic and cortical function such that EEG desynchronization ensues During alert wakefulness Low-voltage, fast (>12 Hz) electrical activity (desynchronized) During deep sleep High-voltage, slow (<3 Hz) electrical activity (synchronized )  

26. Specific rhythmic pattern of the EEG Reflects synchronized waves of excitatory synaptic potentials reaching the cerebral cortex from the thalamus Depend on two important states of the thalamic relay neurons Transmission mode Burst mode

27. During sleep Burst mode Thalamic Relay Neurons Voltage-gated calcium channel Hyperpolarized Calcium current Calcium-activated potassium current Reticular nucleus GABA-B

28. Rhythmic and synchronous firing of thalamic relay neurons ↓ Waves of excitatory postsynaptic potentials in dendrites of cortical neurons ↓ Rhythmic slow waves in EEG Pattern indicating that the thalamus is unable to relay sensory information to the cortex During sleep

29. During wakefulness Cholinergic input from the pedunculopontine and laterodorsal tegmental nuclei in the brain stem and basal forebrain Desynchronized pattern of the EEG Sensory stimuli Transmission mode Thalamic relay nuclei Reticular nucleus Near firing threshold

30. Wakefulness-promoting Neurons Noradrenergic neurons in the locus ceruleus Serotonergic neurons in the dorsal raphe of the brainstem Histaminergic neurons in the tuberomammillary nucleus of the hypothalamus Dopaminergic neurons in the ventral tegmental area, substantia nigra , and ventral periaqueductal area many additional neurons mostly glutamatergic Lateral hypothalamic neurons containing orexin Cholinergic and noncholinergic neurons in the magnocellular basal forebrain nuclei

31. Regulating Sleep-Wake Transitions Reduced activity of hypocretin systems may be partly responsible for inducing sleepiness Ventrolateral preoptic neurons Ascending arousal system GABA and galanin

32. NREM to REM sleep REM-off Ventrolateral periaqueductal graymatter Lateral pontine tegmentum Rem -on Sublaterodorsal nucleus Pre- coeruleus region Dorsal raphe nucleus (DRN) Locus coeruleus (LC) Cholinergic neurons Pedunculopontine (PPT) & Laterodorsal tegmental nuclei (LDT) orexin neurons Ventrolateral preoptic nucleus GABA Glutamate Brainstem and spinal cord Motor manifestations of REM sleep, including atonia GABA Basal forebrain EEG phenomena of REM sleep

33. Modulation of Posture, Gait, and Muscle Tone   Two Reticulospinal Tracts Medial and Lateral reticulospinal tracts

34. Medial Reticulospinal tracts Origin Oral and caudal pontine reticular nuclei Gigantocellular reticular nucleus in the medulla.

35. Medial Reticulospinal Tract Pontine fibres Excite motor neurones of axial and limb muscles Medullary fibres Excite, or inhibit motor neurones of cervical muscles and excite motor neurones of axial muscles.

36. Concerned with Posture Steering of head and trunk movements in response to external stimuli Crude, stereotyped movements of the limbs ( stepping ) Medial Reticulospinal Tract

37. Lateral reticulospinal tract Arise from the medullary reticular formation, mostly from the gigantocellular nucleus Inhibiting excitatory axial extensor muscles Produces loss of motor tone, or atonia Associated with the atonia that occurs in REM sleep(under the control of cholinergic neurons in the pedunculopontine nucleus)

38. Modulation of pain Serotoninergic raphe magnus nucleus in the midline of the rostral medulla Noradrenergic cell groups in the pons Activation of either of these inhibit the transmission of nociceptive information   Endogenous opiates released from enkephalinergic neurons in the periaqueductal gray matter activate the descending modulatory pathway

39. Modulation of autonomic function Ventrolateral medullary reticular formation Gastrointestinal responses (such as swallowing and vomiting) Respiratory activities (including the initiation and modulation of respiratory rhythm, coughing, hiccupping and sneezing) Cardiovascular responses (such as baroreceptor reflexes and responses to cerebral ischemia and hypoxia)

40. Pneumotaxic centre Project to Inspiratory centre in the ventrolateral part of the nucleus solitarius Mixed expiratory- inspiratory centre in the superficial ventrolateral reticular area ↓ Phrenic nucleus and T1-T3 sympathetic preganglionic neurones bilaterally Modulation of autonomic function

41. Hypothalamic, median preoptic and paraventricular nuclei ↓ Lateral parabrachial nucleus and Micturition centres ↓ Bilateral projections in lateral spinal funiculus ↓ Preganglionic parasympathetic neurones in the sacral cord (which innervate the detrusor muscle in the urinary bladder) Nucleus of onuf (which innervate the musculature of the pelvic floor and the anal and urethral sphincters) Modulation of autonomic function

42. Locus Coeruleus Seat of the visceral alerting response Subserves cardiovascular, baroreceptor , chemoreceptor and respiratory reflexes. Terminate bilaterally on sympathetic preganglionic neurones in the thoracic spinal cord Modulation of autonomic function

43. Superficial ventrolateral area Supraoptic and paraventricular hypothalamic nuclei Release of vasopressin from the neurohypophysis . Medullary Noradrenergic Cell Groups A1 And A2 Median eminence Control the release of growth hormone, luteinizing hormone and adrenocorticotrophic hormone (ACTH) Modulation of endocrine function

44. Reticular formation and cerebellum Augments the dorsal and ventral spinocerebellar , cuneocerebellar , accessory cuneocerebellar and trigeminocerebellar tracts Lateral and paramedian reticular nuclei and the nucleus of the pontine tegmentum Ipsilateral vermis , hemisphere and flocculonodular lobule via I/L restiform body (inferior cerebellar peduncle) Contralateral primary motor and sensory neocortices Crossed descending rubrobulbar axons Spinoreticular pathway

45. Monoaminergic neurons in RF Distinct chemoarchitectonic nuclear groups Three catecholaminergic groups Noradrenergic (group A) Adrenergic (group C) Dopaminergic (group A) neurons Serotoninergic neurones (group B cells) Cholinergic neurones (group ch cells )

46. Noradrenergic Cell Groups Two columns, one dorsal and one ventral Medulla Ventral column - associated with the nucleus ambiguus (A1 group) Dorsal column - component of the nucleus of the solitary tract and the dorsal motor vagal nucleus (A2 group) Both groups project to the hypothalamus Control cardiovascular and endocrine functions

47. Pons Ventral column - A5 and A7 Projections to the spinal cord that modulate autonomic reflexes and pain sensation Dorsal column - Locus ceruleus (A6 cell group) Maintains vigilance and responsiveness to unexpected environmental stimuli Extensive projections to the cerebral cortex and cerebellum, as well as descending projections to the brain stem and spinal cord Noradrenergic Cell Groups

48. Adrenergic Cell Groups C1 Rostral extension from the A1 column Project to Spinal cord, particularly to the sympathetic preganglionic column Provide tonic excitatory input to vasomotor neurons Hypothalamus Modulate cardiovascular and endocrine responses

49. C2 adrenergic neurons component of the nucleus of the solitary tract contribute to the ascending pathway to the parabrachial nucleus transmit gastrointestinal information   C3 adrenergic group near the midline at the rostral end of the medulla Adrenergic Cell Groups

50. Dopaminergic neurons Substantia nigra (A9 group) Adjacent retrorubral field (A8 group) Terminates in the striatum Involved in initiating motor responses Ventral tegmental area (A10 group) Innervate the frontal and temporal cortices and the limbic structures of the basal forebrain Implicated in emotion, thought, and memory storage

51. Hypothalamic (A11 and A13 ) in the zona incerta Long descending pathways to the autonomic areas of the lower brain stem and the spinal cord Regulate sympathetic preganglionic neurons A12 and A14 groups Located along the wall of the third ventricle Involved with endocrine control   Also (A15 cells in the olfactory tubercle and A16 in the olfactory bulb) and in the retina (A17 cells) Dopaminergic neurons

52. Serotonergic Cell Groups Along the midline of the brain stem in the raphe nuclei   B1-B3 cell groups along the midline of the caudal medulla descending projections to the motor and autonomic systems in the spinal cord regulating tone in motor systems

53. B4 ( raphe magnus nucleus ) projects to the spinal dorsal horn modulate the perception of pain   B5-B9 ( pons and midbrain ) pontine , dorsal, and median raphe nuclei project to virtually the whole of the forebrain regulate wake-sleep cycles, affective behavior, food intake, thermoregulation, and sexual behavior Serotonergic Cell Groups

54. Dorsal raphe spinal projections Pain-control pathway Intermediate raphe spinal projection Inhibitory, and, in part, modulates central sympathetic control of cardiovascular function Ventral raphe spinal system Excites ventral horn cells and enhance motor responses to nociceptive stimuli Promote the flight and fight response Serotonergic Cell Groups

55. Cholinergic neurons Basal forebrain cholinergic groups Medial septum (MS) (Ch1 group) Nuclei of the vertical and horizontal limbs of the diagonal band ( DBv and DBh ) (Ch2 and Ch3 groups) Nucleus basalis of Meynert (BM) (Ch4 group)

56. Pontine cholinergic neurons Laterodorsal (LDT) (ch5 group) Pedunculopontine (PPT) (ch6 group), tegmental nuclei Provide cholinergic innervation to the brain stem and the thalamus Critical for inducing a state of cortical arousal, both during wakefulness and dreaming Cholinergic neurons

57. Histaminergic Cell Groups Posterior lateral hypothalamus Tuberomammillary nucleus Help maintain arousal in the forebrain

58. RAS & pathological correlates Schizophrenia Intractable schizophrenic patients have a significant increase (> 60%) PPN neurons and dysfunction of NO signaling involved in modulating cholinergic output of the RAS. Post-traumatic stress disorder ,  Parkinson’s Disease ,  REM behavior disorder significant (>50%) decrease in the number of locus coeruleus (LC) neurons, resulting is increased disinhibition of the PPN

59. RAS & pathological correlates Narcolepsy significant down-regulation of PPN output and a loss of orexin peptides, Progressive supranuclear palsy  (PSP) Dysfunction of NO signaling Depression ,  autism ,  Alzheimer's disease ,  attention deficit disorder

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61. Magnocellular Zone Afferents Spinoreticular fibers. Sensory cranial nerves. Cerebellum. Hypothalamus. Basal nuclei. Cerebral cortex: Esp. premotor cortex.

62. Descending Reticular System Inhibitory: Smoothness and accuracy of voluntary movements Reflex movements Regulates muscle tone Maintenance of posture Control vegetative functions Facilitatory : Mantains the muscle tone Facilitates autonomic functions Activates ARAS

63. Other Function Somatic motor control Cardiovascular control Pain modulation - The reticular formation is one means by which pain signals from the lower body reach the cerebral cortex. Sleep and consciousness Habituation Dream