1. Reticular Formation
Dr. G. R. Leichnetz

2. Reticular Formation What is it? What does it do?
The reticular formation is the phylogenetically-oldest part of the CNS that occupies the central core of the brainstem, surrounding principal sensory & motor nuclei and tracts.
It coordinates involuntary functions essential to life:
states of consciousness (sleep & wakefulness, including EEG changes, and associated muscle atonia and eye movements),
visceromotor activities (heart rate, respiration) maintained even when asleep.
It also has descending pathways to the spinal cord that modulate pain and affect muscle tone.

3. The reticular formation occupies the core of the brainstem (midbrain, pons, medulla), surrounding major sensory and motor nuclei and tracts.

4. The reticular formation occupies the central core of the brainstem
The reticular formation occupies the central core of the brainstem. It appears to be homogeneous How is it divided it into separate nuclei?
Reticular Formation

5. CRITERIA FOR SUBDIVIDING THE RETICULAR FORMATION
Subdivided into nuclei on the basis of:
1. Cell size (eg, magnocellular, parvicellular)
2. Brainstem level (eg. nucleus reticularis pontis caudalis)
3. Neurotransmitter Specificity
“A” cell groups: catecholamines (NE, DA) “B” cell groups: indolamines (serotonin) “Ch” cell groups: acetylcholine

6. The reticular formation can be divided into three zones: median (raphe), medial (magnocellular), and lateral (parvicellular) regions M ML L
Barr
The three zones extend rostro-caudally throughout the brainstem. The large cells (magnocellular) of the medial region are found primarily in the pons and rostral medulla.
Niewenhuys

7. MEDIAN RETICULAR FORMATION (Brainstem Raphe)

8. M
The median region of the brainstem reticular formation (brainstem raphe) contains the cell bodies of all of the serotoninergic neurons of the brain, given “B” designation according to the classification by Dahlstrom & Fuxe.
Midbrain raphe B7-B8
Pontine raphe
Medullary raphe B1-B3
Niewenhuys

9. Sup. central raphe nucleus
A mid-sagittal section thru the brainstem shows the serotonergic midline raphe nuclei of the median reticular formation. B7 B8 B5
Sup. central raphe nucleus B3 B1 B2
Carpenter

10. Nuclei are serotonergic.
Median Reticular Formation (Raphe)
Nuclei are serotonergic.
Caudal Midbrain/Rostral Pons Dorsal Raphe Nucleus (B7) Superior Central Nucleus (B8)
Mid-Pons- Nucleus Raphe Pontis (B5)
Rostral Medulla- Nucleus Raphe Magnus (B3)
Mid-Medulla- Nucleus Raphe Obscurus (B2) Nucleus Raphe Pallidus (B1)

11. The pontine raphe projects to the cerebellum.
The midbrain raphe (B7- B8) gives rise to ascending serotonergic projections to higher levels of the CNS (sleep).
The pontine raphe projects to the cerebellum.
The medullary raphe (B1-B3) gives rise to descending serotonergic projections to the spinal cord.
Midbrain raphe (B7, B8)
Medullary raphe (B1, B2, B3)
Niewenhuys

12. Carpenter B3
Serotonergic raphespinal projections descend from the nucleus raphe magnus of the rostral medullary raphe (B3) to laminae I and V of the dorsal horn of the spinal cord, the laminae that receive primary nociceptive (pain) afferents.
The NRM is activated by morphine and modulates pain at the level of the dorsal horn (“gate”).
Serotonergic projections to lamina I & V

13. MEDIAL RETICULAR FORMATION

14. Most of the largest neurons are found in the pons and medulla.
The medial region of the reticular formation contains the largest neurons, ie. is magnocellular.
Most of the largest neurons are found in the pons and medulla.
The nuclei in this region are contiguous and named on the basis of their brainstem level:
Nucleus reticularis gigantocellularis (medulla)
Nucleus reticularis pontis caudalis (caudal pons)
Nucleus reticularis pontis oralis (rostral pons) ML
NRPO
Preponderance of large neurons in pons and rostral medulla
NRPC
NRGC
Niewenhuys

15. Medial Region Magnocellular
Most of the large cells are in the medulla and pons. The nuclei are contiguous and named on the basis of brainstem level.
Nucleus reticularis pontis oralis (NRPO)
Nucleus reticularis pontis caudalis (NRPC)
Nucleus reticularis gigantocellularis
Carpenter

16. Medial Reticular Formation (Magnocellular)
Medulla- Nuc. reticularis gigantocellularis
Caudal Pons- Nuc. reticularis pontis caudalis (contains the physiological PPRF, “horizontal gaze center”)
Rostral Pons- Nucleus reticularis pontis oralis

17. The large cells of the medial region of the reticular formation have long ascending and descending collaterals.
The ascending branches project as far rostrally as the thalamus (reticulothalamics), and the descending branches project caudally into the spinal cord (reticulospinals).
Thus these cells can have a broad influence over the entire CNS neuraxis.
Cytology
Collaterals to intralaminar nuclei of the thalamus
Collaterals to brainstem and spinal cord
Large cell in the medial magnocellular reticular formation

18. Descending branches of large neurons in the pontine and medullary reticular formation (NRPC, NRG) constitute the classical reticulospinal tracts that project to the medial part of the ventral horn to affect muscle tone.
In general, pontine reticulospinals are excitatory, and medullary reticulospinals are inhibitory, on spinal motoneurons; particularly those in the medial ventral horn.
NRPC
NRG
Medullary reticulospinal tract
Pontine reticulospinal tract
Carpenter

19. Ascending reticulothalamics from large neurons in the medial pontine and medullary reticular formation
Ascending branches from large neurons in the medial region of the pontine and medullary reticular formation project as far rostrally as the thalamus (reticulothalamics), terminating primarily in the intralaminar nuclei.
These reticulothalamics were originally thought to be the substrate for the reticular activating system of Moruzzi and Magoun.
Carpenter

20. The concept of “reticular activating system” (Moruzzi & Magoun) held that the medial brainstem reticular formation activated the cortical EEG (waking state) thru projections to the intralaminar nuclei of the thalamus, which projected diffusely to broad areas of the cerebral cortex.
Gross stimulation produced awake state; large lesions of the medial reticular formation prevented the animal from waking up… leading to the concept that the reticular formation contained centers essential for cortical EEG activation.

21. More recent evidence, however, shows that all three regions of the reticular formation contain nuclei that affect the sleep/waking cycle: midbrain raphe (serotonin; EEG synchronization, slow wave sleep); locus ceruleus (norepinephrine; EEG desynchronization, waking state); pedunculopontine nucleus (acetylcholine; onset of REM sleep).

22. The medial region of the reticular formation also contains the premotor centers for control of saccadic eye movements. The riMLF, INC in the rostral midbrain- vertical saccades. The PPRF in the caudal pons (NRPC)- horizontal saccades.
INC
riMLF
PPRF

23. The rostral interstitial nucleus of the MLF (riMLF), the center for vertical downward saccades, is located in the rostralmost midbrain reticular formation where it merges with the subthalamic region.
Prerubral fields
riMLF
Subthalamic Nucleus RN
The center for vertical gaze, (riMLF) in the monkey lies in the most rostral midbrain reticular formation in the prerubral fields.
Parvicellular red nucleus

24. The interstitial nucleus of Cajal contains premotor neurons that project to cell groups in the oculomotor nuclei (superior rectus and inferior oblique) for vertical upward eye movements.
INC
Oculomotor Complex

25. The physiological area for control of horizontal saccades, PPRF, is located within the nucleus reticularis pontis caudalis (NRPC) in the medial pontine reticular formation at the level of the abducens nucleus. VI
PPRF (NRPC)
Large neurons in the PPRF have ascending branches to abducens nucleus, and descending projections to cervical spinal cord (gaze)

26. LATERAL RETICULAR FORMATION

27. The region contains NE and ACh neurotransmitter-specific cell groups.
The lateral region of the reticular formation contains predominantly small cells (parvicellular).
The region contains NE and ACh neurotransmitter-specific cell groups.
NE cell groups A5, A7 have ascending branches to the hypothalamus, and (along with A1-A3) descending branches to the spinal cord involved in visceromotor activities.
The locus ceruleus (A6) projects throughout CNS, produces waking state.
Ch5 cell group (pedunculopontine nucleus) gives rise to cholinergic trigger for the onset of REM sleep. L
Ch5 A6
A5-A7
Small neurons in cell groups identified by neurotransmitter- specificity
A1-A3
Niewenhuys

28. At the level of the rostral pons, the cholinergic pedunculopontine nucleus (Ch5) and noradrenergic locus ceruleus (A6) are located in the lateral region of the rostral pontine reticular formation.
Carpenter

29. The locus ceruleus (A6) is located in the periaqueductal gray of the rostral pons. It contains neuromelanin pigment which is the byproduct of catecholamine synthesis (NE).
IVth ventricle
Its axons have long ascending and decsending branches which are highly collateralized throughout the entire CNS neuraxis; effects activation of the entire CNS during stress (anxiety).

30. The locus ceruleus gives rise to ascending projections to all higher levels of the CNS, and descending projections to the lower brainstem and spinal cord.
Its connections facilitate broad CNS activation during “fight or flight.”
Locus ceruleus A6
Niewenhuys

31. Other NE cell groups (A1-A3, A5, A7) in the lateral pontine and medullary reticular formation have connections related to control of visceromotor (autonomic) activities.
Hypothalamus
A5 A7
A1-A3
Niewenhuys

32. Cell group A5, located in the lateral region of the caudal pontine reticular formation, is concerned with the control of blood pressure. A5

33. NE cell group A5 gives rise to ascending projections to the hypothalamus, and descending projections to autonomic centers (eg. dorsal motor nucleus of vagus, intermediolateral cell column (sympathetics) of the spinal cord) that affect blood pressure. A5
(to hypothalamus) A5
Descending projections
Carpenter

34. The lateral medullary reticular formation contains the vital dorsal and ventral respiratory areas. The DRA concerned with chemical aspects of respiration (pCO2) and the VRA the mechanical aspects of respiration (inspiration, expiration).
Solitary nucleus
DMV
DRA is in the reticular formation surrounding the solitary nucleus
DRA
VRA is in the reticular formation surrounding the nucleus ambiguus; contains NE cell groups A1-A3
VRA

35. Lateral Reticular Formation (parvicellular)
Dorsolateral Pons Locus Ceruleus (NE, A6) Pedunculopontine Nucleus (ACh, Ch5)
Caudal Pons- Pressor Area (NE, A5)
Medulla- Dorsal Respiratory Area Ventral Respiratory Area

36. NE Cell Groups A5, A7 A6
Ch5
NE Cell Groups A1-A3