Exploring the Functions of the Reticular Formation

The reticular formation is a complex network of nuclei and neurons involved in many functions, such as sensory processing, pain modulation, arousal or the sleep-wake cycle. Its abnormal functioning can result in clinical symptoms of diseases such as Schizophrenia, Parkinson’s disease or Post Traumatic Stress Disorder. In this blog post, we'll delve into explaining the reticular formation, exploring how it influences various aspects of brain function and how its dysfunction can contribute to these neurological disorders.
Frederika Malichová

Frederika Malichová

Neuroscientist at the University Of Cambridge.

A 3D image of the brain.

What is the Reticular Formation?

The reticular formation is a complex network of nuclei and neurons. It is located in the brainstem, specifically in the midbrain, pons, and medulla oblongata. It serves as a major integration and relay centre for various brain systems involved in functions necessary for survival.

The reticular formation plays a role in coordinating and influencing different regions of the central and peripheral nervous systems. The functions of the reticular formation include sensory processing, pain modulation, arousal, sleep-wake cycle regulation, and motor control.

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The reticular formation also interacts with other brain regions, such as the thalamus and neocortex and controls their states of activation and deactivation.

However, due to its diffuse and widespread nature, studying the reticular formation presents challenges, and there is still much to be discovered about its precise functions and mechanisms [1].

Functions of the Reticular Formation

Reticular Formation and Sensory Processing

Studies have shown that reticular formation is important for sensory information encoding, modulation, and transmission.

It is involved in the processing of auditory stimuli, somatosensory information, and even sensory input from the male genitalia.

Overall, the reticular formation is a key component of the sensory processing network in the brain [2, 3].

Reticular Formation and Pain Modulation

The reticular formation contains various areas that receive nociceptive input (pain signals) from the spinal cord and are involved in the transmission and modulation of pain signals.

The reticular formation can trigger alert reactions and generate protective/defense responses to pain.

It also participates in the control of vital functions, such as cardiovascular control, which can be affected by pain.

Additionally, specific areas within the reticular formation, such as the rostroventromedial medulla (RVM) and the caudal ventrolateral medulla (VLM), are involved in bidirectional pain control. These areas have distinct neuronal populations that contribute to antinociceptive or pronociceptive behavioural responses.

The reticular formation, particularly the RVM-VLM-DRt (dorsal reticular nucleus) triad, represents a key component of the "dynamic pain connectome". The dynamic pain connectome is a network of brain regions and their functional connectivity that are involved in the perception and processing of pain. [4]

Furthermore, the RF is also involved in the emotional and cognitive modulation of pain. [5, 6]

Reticular Formation and Arousal

The network of neurons within the reticular formation extends into the thalamus and basal forebrain, establishing an additional function of the reticular formation: arousal.

It receives sensory input from both external and internal stimuli and various parts of the body, and relays it to the cortex, contributing to wakefulness and alertness. In particular, the reticular formation influences arousal through its activation of the ascending reticular activating system.

Different components of the reticular formation, such as the glutamatergic neurons in the parabrachial nucleus and the cholinergic neurons are involved in promoting and maintaining arousal.

The ascending reticular activating system consists of neural pathways that project from the reticular formation to various regions of the brain, including the thalamus and cortex.

These pathways release neurotransmitters, such as glutamate, acetylcholine, dopamine, norepinephrine, serotonin, and histamine, which play a role in promoting both arousal and wakefulness [7, 8, 9, 10].

Sleep-Wake Cycle Regulation

The sleep-wake cycle is a complex physiological process that is tightly regulated by many brain structures.

The reticular activating system (RAS), a component of the reticular formation, plays a pivotal role in promoting wakefulness and maintaining an alert state.

To achieve its wakefulness-promoting function, the reticular activating system releases several neurotransmitters, including acetylcholine, norepinephrine, serotonin, and histamine. These neurotransmitters are essential in promoting wakefulness and arousal, ensuring that an individual remains alert during the day.

The reticular formation also interacts with other brain regions such as thalamus, hypothalamus and basal forebrain. The thalamus acts as a relay station for sensory information, and it has a dual role in regulating sleep and wakefulness. During sleep, the reticular formation sends inhibitory signals to the thalamus. This reduces sensory input and contributes to the establishment of a restful state, essential for quality sleep.

Furthermore, the reticular formation's interactions with the hypothalamus and basal forebrain help coordinate the transitions between wakefulness and sleep. These interactions ensure a smooth shift between the two states, allowing the body to adapt to changing conditions and rest as needed.

Moreover, the reticular formation receives input from the suprachiasmatic nucleus, which serves as the master circadian clock in the brain. This input helps regulate the timing of sleep and wakefulness, ensuring that the sleep-wake cycle aligns with the body's internal circadian rhythms [11].

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Reticular Formation and Neurological Disorders

It is believed that reticular formation plays a significant role in clinical symptoms of diseases like Schizophrenia, Post-Traumatic Stress Disorder (PTSD), REM behaviour disorder, or Parkinson’s disease.

In schizophrenia, the abnormal activation of the reticular formation is believed to cause sleep-wake disturbances and a decrease in REM sleep. Adding to this, post-mortem analysis of the brains of patients suffering from schizophrenia showed that there was a greater number of neurons in one of the nuclei of the reticular formation than in the brains of healthy controls [11].

In Post-Traumatic Stress Disorder, it has been proposed that patients with PTSD with anxiety symptoms had a decrease of neurons in locus coeruleus, which is a part of the reticular activating system involved in the stress and panic response [11].

In Parkinson’s disease, similar to PTSD, the reticular formation is believed to play a role in motor and sleep-wake dysfunction. The patients also show loss of neurons in the locus coeruleus, REM sleep disorders and sleep-wake disturbances [11].

REM Sleep Disorder is commonly diagnosed and observed prior to the onset of Parkinson’s disease [11].


In summary, the reticular formation is essential for many brain activities, from managing how we process pain and sensory information to regulating our sleep and alertness. Despite its complexity, research is gradually revealing how it works and its role in various brain disorders. Understanding the reticular formation is key to better treatments and insights into brain health.

Frederika Malichová

Frederika Malichová

Frederika is a postgraduate researcher at the University of Cambridge, where she investigates new biomarkers for Frontotemporal Dementia and other tauopathies. Her research has been published at prestigious conferences such as the Alzheimer’s Association International Conference 2023. She obtained her BSc in Biomedical Sciences from UCL, where she worked closely with the UK Dementia Research Institute.