Pedunculopontine and Laterodorsal Tegmental Nuclei

Anatomy

• At the midbrain–pons junction: the PPN around and lateral to the superior cerebellar peduncle; the LDT more medially, at the caudal end of the PAG, near the floor of the fourth ventricle.
• Cholinergic neurons form groups Ch5 (PPN) and Ch6 (LDT); glutamatergic and GABAergic neurons are interspersed.
• In the Harvard AAN atlas the PPN appears as the “pedunculotegmental nucleus (PTg)”.
• Connections: thalamus, basal ganglia (GPi, subthalamic nucleus, substantia nigra), VTA, reticular formation, spinal cord.

Functions

• Wakefulness and REM sleep: cholinergic fibers to the thalamus switch on thalamocortical activity; they take part in initiating REM sleep.
• Attention and sensory gating: contribution to inhibition of the startle reflex by a prepulse (prepulse inhibition).
• Reward and motivation: the LDT and PPN excite dopamine neurons in the VTA and substantia nigra, supporting phasic dopamine release.
• Movement: the PPN is part of the mesencephalic locomotor region; initiation of gait and postural control.

Connections and chemistry

• PPN/LDT → thalamus (wakefulness, thalamocortical activity)
• LDT → VTA, PPN → substantia nigra (excitation of dopamine neurons)
• PPN ↔ basal ganglia (GPi, subthalamic nucleus): movement
• PPN → reticular formation and spinal cord (posture, gait)
• Acetylcholine (nicotinic and muscarinic receptors), glutamate, GABA

Development

Developmental course through childhood and adolescence.

• About half of the newborn’s sleep is REM sleep; it has been proposed that REM activity stimulates the developing brain from within (Roffwarg et al., 1966).
• The proportion of REM sleep decreases through childhood, and sleep–wake transitions consolidate.

Clinical

• Narcolepsy type 1: with orexin loss, brainstem circuits that regulate REM sleep go unchecked; cataplexy, sleep paralysis, hypnagogic hallucinations.
• Nightmare disorder and post-traumatic sleep disturbances: changes in REM sleep regulation.
• Schizophrenia: disturbed sensory gating (PPI); postmortem studies have reported more cholinergic neurons in the PPN/LDT.
• Anticholinergic drugs (e.g. diphenhydramine, some antipsychotics, tricyclics) can disrupt sleep architecture, memory and attention, and cause delirium.
• Freezing of gait in Parkinson’s disease: the PPN is being studied as a deep brain stimulation target (adults).

Treatment

This region from the perspective of medication, psychotherapy and neuromodulation. Letter badges are evidence levels.

• Anticholinergic burden: combining several anticholinergic drugs (diphenhydramine, hydroxyzine, tricyclics, some antipsychotics) impairs attention, memory and sleep architecture; the risk of delirium is higher in children and in those with developmental disabilities. A medication review is recommended. B
• REM-related symptoms of narcolepsy (cataplexy, sleep paralysis) are reduced by sodium oxybate and pitolisant; details on the hypothalamus card. A
• PPN deep brain stimulation: experimental in adults for freezing of gait in Parkinson’s disease. C

Assessment

Neuropsychological tasks and measures that probe this region's function.

• Polysomnography: REM sleep latency and duration
• Prepulse inhibition (PPI) and the startle reflex
• Gait and balance analysis (in movement disorders)

Lesions and damage

Clinical findings expected with damage or dysfunction.

• Bilateral PPN damage: reduced wakefulness and gait disturbance; reduced REM sleep in animal studies.
• Lesions of the pontomesencephalic tegmentum can impair consciousness (the arousal network).

In the model

How this structure is defined in the 3D model, and the data source.

Harvard AAN v2.0 pedunculotegmental (PTg, i.e. PPN) and laterodorsal tegmental (LDTg) labels (right/left), in the same color. The atlas’s separate “PTg_L” file contains both sides, so the combined label file was used.

References

Full citations for the card; links go to the paper (DOI) or a PubMed search.

1. Roffwarg HP, Muzio JN, Dement WC. Ontogenetic development of the human sleep-dream cycle. Science 1966;152(3722):604–619. DOI: 10.1126/science.152.3722.604