1. Brain stem modulation of sensation, movement, and consciousness
From Ch. 45
“Principles of Neural Science”, 4th Ed.
Kandel et al.

2. The brain stem

3. 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
Local-circuit interneurons
Reflexive and stereotyped behaviors involving face and head:
Chewing, swallowing and vomiting
Respiratory activities (coughing, hiccups and sneezing)
Cardiovascular responses
Long projection systems
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
Brain stem

4. 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.

5. RF subsystems Six neurotransmitter systems Choline (Ch)/ Acetylcholine
Norepinephrine / noradrenaline (A)
Medulla: A1,A2
Pons: A5, A6, A7
Epinephrine / Adrenaline (C)
Medulla: C1,C2
Dopamine (A8-A17)
Serotonin (B)
Medulla (B1-B3)
Pons and midbrain (B4-B8)
Choline (Ch)/ Acetylcholine
Histamine (E)
(A)
(B)

6. 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

7. Noradrenergic (NA) cell groups
Locus ceruleus
Located in the dorsal wall of the rostral pons
Contains the largest collection of NA cells
Consists of ~ 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

8. Dopaminergic cell groups
Hypothalamic DA neurons
SN and VTA DA neurons
Largest DA groups of neurons
Substantia nigra (A8, A9)
Ventral tegmental area (A10)
Other:
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
Nigrostriatal pathway (Globus pallidus, Thalamus)
Mesocortical pathway (Prefrontal cortex, ACC)
Mesolimbic pathway (Nac, Hipp)
Functions
Initiation of motor responses
Emotions, thought and memory
Reward system/ reinforcement (drug addiction)
Regulation of sympathetic preganglionic neurons
Eendocrine control

9. Serotonergic cell groups
The raphe nuclei (RN)
Upper/ rostral RN in pons and midbrain
Raphe pontis (B4-B6)
Median raphe (B8)
Dorsal raphe (B7)
Lower/ posterior RN in medulla
Raphe magnus (B1)
Raphe pallidus (B2)
Raphe obscurus (B3)
Projections of RN
Rostral RN projects to forebrain
Posterior RN projects to the brain stem and spinal cord
Functions of the rostral RN
Regulation of the sleep-wake cycle
Affective behavior
Functions of the posterior RN
Regulation of motor tone and pain

10. Cholinergic cell groups
Ch is used by both somatic and autonomic motor neurons
Loci in midbrain
Pedunculopontine nucleus (PPT), Ch6
Laterodorsal tegmental nucleus (LDT), Ch5
Projections
Reticular formation
Thalamus
Lateral hypothalamus
Functions
Cortical arousal during wakefulness and dreaming (ascending arousal system)
Regulation of sleep-wake cycle
Enhancement of incoming sensory stimuli
Ascending arousal system

11. 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

12. 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:
Chewing, swallowing and vomiting
Respiratory activities (coughing, hiccups and sneezing)
Cardiovascular responses
Long projection systems
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
Brain stem

13. 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
Origins from pontine reticular formation
Function: facilitation of spinal motor neurons in legs for postural support and patterned stereotyped movements
Lateral reticulospinal tracts
Origins from medial medullary reticular formation
Function: inhibits cranial and spinal motor neurons => motor tone

14. Ascending arousal system
Two ascending branches
Thalamus
Lateral hypothalamus
Multiple neurotransmitter systems
Functions:
Increased arousal: wakefullness and vigilance
Increased neuronal responses to sensory stimuli
Lesions
Disruption impairs consciousness

15. Electroencephalography
Consciousness
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
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

16. Brain stem lesions

17. 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.