brain stem · caudal medulla to the rostral midbrain and continuous with the zona incerta of the...

Brain stemBrain stem

Reticular formationReticular formation

DefinitionDefinition

�� MMass of neurons and nerve fibers extending from the ass of neurons and nerve fibers extending from the

caudal medulla to the rostral midbrain and continuous caudal medulla to the rostral midbrain and continuous

with the zona incerta of the subthalamus and midline, with the zona incerta of the subthalamus and midline,

intralaminar and reticular nuclei of the thalamusintralaminar and reticular nuclei of the thalamus

�� OOrganized into definite nuclear groups with known rganized into definite nuclear groups with known

afferent and efferent connections afferent and efferent connections

�� As a whole, the reticular formation comprises a neural As a whole, the reticular formation comprises a neural

system with multiple inputs and multisynaptic system of system with multiple inputs and multisynaptic system of

impulse conductionimpulse conduction

Organization of Organization of reticular formation reticular formation

�� Median rapheMedian raphe nuclear groupnuclear group

�� Paramedian reticularParamedian reticular nuclear groupnuclear group

�� Medial reticularMedial reticular nuclear groupnuclear group

�� Lateral reticularLateral reticular nuclear groupnuclear group

Each nuclear group is represented at the level of Each nuclear group is represented at the level of

midbrainmidbrain

ponspons

medullamedulla

Reticular Reticular nnucleiuclei

(MCP)

Reticular Reticular nnuclei uclei

Cuneiform

Subcuneifor

m

Dorsal Raphe

(nucleus

supratrochlearis)

Superior central

(Bekhterew)

Midbrain

Parabrachial

Pedunculop

ontine

Reticulotegm

entalRostral pons–

caudal

midbrain

Reticularis

parvocellular

is

Reticularis pontis

caudalis

Reticularis

pontis oralis

Raphe pontisPons

Paramedian

reticular

Raphe magnusRostral medulla

caudal pons

Reticularis

parvocellular

is

Reticularis

lateralis

Reticularis giganto

cellularis

Raphe obscurus

Raphe pallidusMedulla

LateralMedialParamedianMedian Raphe

Reticular formation Reticular formation –– summary of functionssummary of functions

Purves, et al, Neuroscience, 3rd ed.

Median raphe nuclei

rostral raphe nuclei →

reticular activating

system (wakefulness,

alertness, and sleep)

caudal raphe nuclei →

pain mechanisms

Pain control

pathways &

reticular formation

Ascending pain pathways

Descending systems modulate the transmission of

ascending pain signals

Kandel, Schwartz, Jessell; Principles of

Neural Science, 4th ed. Purves, et al, Neuroscience, 3rd ed.

Descending analgesic pathways activate enkephalin-

containing local circuit neurons

Purves, et al, Neuroscience, 3rd ed.

SER, NA

Glu, NP

morphine

acts here

Medial reticular

nuclei

Gigantocellular nucleus

cuneiform & subcuneiform nuclei

ascending projections

→ consciousness and

alertness

descending projections →

motor control

Premotor cortex regulates posture via the Premotor cortex regulates posture via the

reticular formationreticular formation

Purves, et al, Neuroscience, 3rd ed.

Integration of direct and indirect Integration of direct and indirect

neocortical pathways to spinal cordneocortical pathways to spinal cord

Cortex

Brainstem

Spinal cord

Limb fine

movementsPostural

adjustments

to movements

Paramedian reticular (precerebellar) nuclei

Cortex

Cerebellum

Spinal cord/vestibular nuclei

control of

movements

Paramedian

reticular nuclei

Lateral reticular nuclei

�� Pedunculopontine Pedunculopontine –– connections with connections with

cortex & substantia nigra cortex & substantia nigra →→ locomotor locomotor

centercenter

�� PParabrachial nucleus arabrachial nucleus –– connections withconnections with

amygdala, nucleus solitariusamygdala, nucleus solitarius, ,

hypothalamushypothalamus →→ autonomic functionautonomic function

�� N. N. parvocellularis and lateralis constitute parvocellularis and lateralis constitute

the receptive component of reticular the receptive component of reticular

nuclei nuclei –– receive from ascending sensory receive from ascending sensory

systems, project to cortex & medial systems, project to cortex & medial

reticular groupreticular group

Reticular formation Reticular formation –– summary of functionssummary of functions

Purves, et al, Neuroscience, 3rd ed.

Reticular formation Reticular formation –– summary of major pathwayssummary of major pathways

Noradrenergic neurons

Reticulospinal tractSerotonergic neurons

CChemically specified systemshemically specified systems of the reticular of the reticular

formationformation�� CholinergicCholinergic ssystemystem (groups Ch1(groups Ch1--Ch6) Ch6) -- AchAch

�� LLocations ocations

�� pontomesencephalic junction pontomesencephalic junction –– e.g. pedunculopontine nucleuse.g. pedunculopontine nucleus

�� basal forebrainbasal forebrain -- nucleus basalis of Meynert nucleus basalis of Meynert

�� Function Function -- cortical arousal cortical arousal -- wakefulness and REM sleep wakefulness and REM sleep

�� MonoaminergicMonoaminergic System System –– NE, E, Ser, DopNE, E, Ser, Dop

�� Serotonergic neurons Serotonergic neurons ((groups B1 to B9groups B1 to B9) ) –– most median raphe nuclei most median raphe nuclei →→destruction of destruction of thesethese neurons leads to insomnianeurons leads to insomnia; mood regulation; mood regulation

�� Noradrenergic neurons Noradrenergic neurons -- attention, sleepattention, sleep--wake state and moodwake state and mood

�� locus ceruleus (group A6locus ceruleus (group A6); ); (Latin, (Latin, ““dark blue placedark blue place””) )

�� lateral tegmental norepinephrine system (groups A1 to A7)lateral tegmental norepinephrine system (groups A1 to A7)

�� Adrenergic neurons Adrenergic neurons (groups C1(groups C1--C2)C2)-- a minor component of the a minor component of the monoaminergic system monoaminergic system

�� Dopaminergic neurons Dopaminergic neurons –– most are in the midbran most are in the midbran (ventral tegmental area(ventral tegmental area))

�� mesostriatal (mesostriatal (== nigrostriatal) pathway nigrostriatal) pathway –– to substantia nigra to substantia nigra →→ PD!!!PD!!!

�� mesolimbic mesolimbic pathway pathway –– to the limbic system to the limbic system →→ ooveractivity veractivity inin schizophrenischizophreniaa

�� mesocortical mesocortical –– to prefrontal cortex to prefrontal cortex →→ cognitive deficits in PDcognitive deficits in PD

DDirect (aminergic) and indirect (cholinergic) irect (aminergic) and indirect (cholinergic)

cortical arousal system cortical arousal system regulate sleepregulate sleep

MonoMonoaminergic nuclei promote wakefulness via facilitation of the aminergic nuclei promote wakefulness via facilitation of the

cerebral cortex and inhibition of sleepcerebral cortex and inhibition of sleep--promoting neurons promoting neurons

(hypothalamus)

ComaComa

�� Damage to the reticular formation at the level of Damage to the reticular formation at the level of

thethe rostral pons and caudal medulla may lead to rostral pons and caudal medulla may lead to

coma orcoma or akinetic mutism (coma vigil). An EEG akinetic mutism (coma vigil). An EEG

similar to thesimilar to the slow phase of the sleep slow phase of the sleep

characterizes this condition,characterizes this condition, with no appreciable with no appreciable

change in the autonomic andchange in the autonomic and somatomotor somatomotor

reflexes or eye movemenreflexes or eye movementt

�� Coma might be reversibleComa might be reversible

Brain death Brain death

�� SState of irreversible brain damage so severe that normal tate of irreversible brain damage so severe that normal respiration and cardiovascular function can no longer respiration and cardiovascular function can no longer be maintainedbe maintained

�� In modern clinical medicine, cessation of life is equated In modern clinical medicine, cessation of life is equated with brain death rather than with cessation of heart beat with brain death rather than with cessation of heart beat

�� CCriteriariteria ((ccomatose patients fulfillomatose patients fulfillinging thethesese criteria are criteria are considered deadconsidered dead))

�� Unresponsiveness to external stimuliUnresponsiveness to external stimuli

�� Absence of spontaneous breathingAbsence of spontaneous breathing

�� Dilated fixed pupilsDilated fixed pupils

�� Absence of brain stem reflexes (corneal, gag, vestibuloocular)Absence of brain stem reflexes (corneal, gag, vestibuloocular)

�� No recognizable reversible cause for the comaNo recognizable reversible cause for the coma

�� Flat electroencephalogram (absence of electrical activity)Flat electroencephalogram (absence of electrical activity)

�� Nonfilling of cerebral vessels in arteriography or radioisotope Nonfilling of cerebral vessels in arteriography or radioisotope imaging imaging

Reticular formation in midbrainReticular formation in midbrain

Reticular formation in ponsReticular formation in pons

Reticular formation in medullaReticular formation in medulla

Development of reticular formationDevelopment of reticular formation

Modified from Bayer SA et al. Neurotoxicology 14:83–144, 1993