Brain stem modulation of
sensation, movement, and
consciousness
From Ch. 45
“Principles of Neural Science”, 4th Ed.
Kandel et al.
The brain stem
Reticular formation (RF)
•
RF is a set of interconnected nuclei that are located
throughout the brain stem
•
One of the phylogenetically oldest portions of the brain
•
Local projections
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–
Local-circuit interneurons
Reflexive and stereotyped behaviors involving face and head:
•
•
•
•
Long projection systems
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–
•
Chewing, swallowing and vomiting
Respiratory activities (coughing, hiccups and sneezing)
Cardiovascular responses
Brain
stem
Ascending to cortex
Descending to spinal cord
Functions of long projections
–
–
–
–
Pain/ sensory perception
Posture
Wakefulness/ arousal
Filtering incoming stimuli to discriminate irrelevant background stimuli
http://www.colorado.edu/intphys/Class/IPH
Y3730/image/figure5-29.jpg
Reticular formation (RF)
• The ascending reticular formation (the reticular activating system)
– Responsible for the sleep-wake cycle
– Mediates various levels of alertness and consciousness.
– Projects to the mid-line group of the thalamus, which also plays a role in wakefulness.
From there, information is sent to the cortex.
• The descending reticular formation
– Involved in posture and equilibrium as well as autonomic nervous system activity.
– Involved in sensory and motor modulation.
– It receives information from the hypothalamus.
RF subsystems
• Six neurotransmitter systems
– Norepinephrine / noradrenaline (A)
• Medulla: A1,A2
• Pons: A5, A6, A7
(A)
(B)
– Epinephrine / Adrenaline (C)
• Medulla: C1,C2
– Dopamine (A8-A17)
– Serotonin (B)
• Medulla (B1-B3)
• Pons and midbrain (B4-B8)
– Choline (Ch)/ Acetylcholine
– Histamine (E)
Noradrenergic/ adrenergic neurons in medulla
Dorsal
Ventral
A1/ C1: near nucleus ambiguus; A2/ C2: Nucleus of the solitary tract/ dorsal motor vagal nucleus; LC (A6): Locus ceruleus
A1/ A2 groups project to hypothalamus and controls cardiovascular and endocrine functions
A5/A7 are located in the pons and mainly projects to the brain stem and spinal cord where they modulate autonomic reflexes and pain
C1 neurons projects to hypothalamus where they modulate cardiovascular and endocrine functions
C1 neurons also projects to the spinal cord where they provide tonic excitatory input to vasomotor neurons
C2 neurons projects to the parabrachial nucleus providing visceral input
Noradrenergic (NA) cell groups
• Locus ceruleus
– Located in the dorsal wall of the rostral pons
– Contains the largest collection of NA cells
– Consists of ~ 10.000 neurons
– Projects to every major region of the brain
and spinal cord
– Maintains vigilance and responsiveness to
novel/ unexpected stimuli
– Influences arousal including sensory
perception and muscle tone
– Is involved in physiological stress responses
Dopaminergic cell groups
•
Largest DA groups of neurons
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–
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Substantia nigra (A8, A9)
Ventral tegmental area (A10)
Other:
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•
•
•
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Dorsal hypothalamus (A11, A13) => spinal cord
Tuberoinfundibular hypothalamic neuroendocrine system (A12, A14)
Olfactory tubercke (A15) and bulb (A16)
Retina (A17)
Ascending input to the cerebral cortex and the
basal ganglia
–
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Nigrostriatal pathway (Globus pallidus, Thalamus)
Mesocortical pathway (Prefrontal cortex, ACC)
Mesolimbic pathway (Nac, Hipp)
Functions
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SN and VTA DA neurons
Initiation of motor responses
Emotions, thought and memory
Reward system/ reinforcement (drug addiction)
Regulation of sympathetic preganglionic neurons
Eendocrine control
Hypothalamic DA neurons
Serotonergic cell groups
•
The raphe nuclei (RN)
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Upper/ rostral RN in pons and midbrain
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•
•
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Lower/ posterior RN in medulla
•
•
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Rostral RN projects to forebrain
Posterior RN projects to the brain stem and spinal cord
Functions of the rostral RN
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–
•
Raphe magnus (B1)
Raphe pallidus (B2)
Raphe obscurus (B3)
Projections of RN
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•
Raphe pontis (B4-B6)
Median raphe (B8)
Dorsal raphe (B7)
Regulation of the sleep-wake cycle
Affective behavior
Functions of the posterior RN
–
Regulation of motor tone and pain
Cholinergic cell groups
• Ch is used by both somatic and autonomic
motor neurons
• Loci in midbrain
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Pedunculopontine nucleus (PPT), Ch6
Laterodorsal tegmental nucleus (LDT), Ch5
• Projections
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•
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Reticular formation
Thalamus
Lateral hypothalamus
• Functions
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•
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Cortical arousal during wakefulness and dreaming
(ascending arousal system)
Regulation of sleep-wake cycle
Enhancement of incoming sensory stimuli
Ascending arousal system
Histaminegic cell groups
• All histaminergic neurons are located in the
posterior hypothalamus
– Tuberomammillary nucleus (TMN)
•
•
Ventrolaterally
Dorsomedially
• Projects to all major parts of cerebral cortex and
spinal cord
• Functions
– Regulation of behavioral arousal
– Regulation of sleep
– Circadian rhythm
Reticular formation (RF): again
•
RF is a set of interconnected nuclei that are
located throughout the brain stem
•
Local projections
–
–
Local-circuit interneurons
Reflexive and stereotyped behaviors involving face and
head:
•
•
•
•
Long projection systems
–
–
•
Chewing, swallowing and vomiting
Respiratory activities (coughing, hiccups and sneezing)
Cardiovascular responses
Brain
stem
Ascending to cortex
Descending to spinal cord
Functions of long projections
–
–
–
–
Pain/ sensory perception
Posture
Wakefulness/ arousal
Filtering incoming stimuli to discriminate irrelevant
background stimuli
http://www.colorado.edu/intphys/Class/IPH
Y3730/image/figure5-29.jpg
Descending projections
• Pain modulation
– Spinal dorsal horn
•
•
Raphe magnus (serotonergic) in rostral medulla<= opiodergic periaqueductal grey
Noradrenergic neurons in pons
– Function: descending inhibition of nociceptive transmission
• Posture, gait and muscle tone modulation
– Medial reticulospinal tracts
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Origins from pontine reticular formation
Function: facilitation of spinal motor neurons in legs for postural support and patterned stereotyped
movements
– Lateral reticulospinal tracts
•
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Origins from medial medullary reticular formation
Function: inhibits cranial and spinal motor neurons => motor tone
Ascending arousal system
• Two ascending branches
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Functions:
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Thalamus
Lateral hypothalamus
Multiple neurotransmitter systems
Increased arousal: wakefullness and vigilance
Increased neuronal responses to sensory stimuli
Lesions
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Disruption impairs consciousness
Electroencephalography
•
Consciousness
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Being aware of oneself and one’s place in the enviroment
The ability to respond/ orient appropriately to environmental
stimuli
It is not sufficient to say that consciousness result from the
summed cortical activity since the brain stem is crucial
Transection of the brain stem below the level of the rostral pons
does not affect consciousness
Acute transection rostral to inferior colliculus result in coma
(unarousability)
EEG is important in assessment of wakefulness
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Reflects firing patterns in the thalamocortical pathway
(transmission and burst mode)
Wakefulness: low voltage, high frequency, desynchronized
patterns
Coma: high voltage , low frequency, synchronized patterns as in
sleep
Burst mode: hyperpolarized neurons respond to brief depolarization with bursts
Transmission mode: A depolarized mode where incoming EPSP can drive the
neuron to fire in a pattern that reflects the sensory stimuli… single AP produced
Brain stem lesions
• Respiratory patterns indicates the level of
lesion
A. Waxing-and-waning pattern with apnea: diffuse
forebrain depression due to metabolic
encephalopathy e.g. liver failure
B. Hyperventilation: injury to mid brain
C. Apneusis: injury to rostral pons – breathing halts
briefly at full inspiration
D. Ataxic breathing: injury to the lower pons or
upper medulla – irregular and uneven depth of
breathing
E. Complete apnea (respiratory arrest): bilateral
lesion of the ventrolateral medulla
ETC.
• Integration of sensory input and motor output occurs in the
brain stem as well. For example, the midbrain integrates
auditory input and motor responses in the eye.
• The brain stem also contains specific pathways which move
information from the spinal level up to the brain and other
descending pathways from the brain.