24 Reticular formation

Introduction

The reticular formation is phylogenetically a very old neural network, being a prominent feature of the reptilian brainstem. It originated as a slowly conducting, polysynaptic pathway intimately connected with olfactory and limbic regions. The progressive dominance of vision and hearing over olfaction led to localization of sensory and motor functions within the tectum of the midbrain. Direct spinotectal and tectospinal tracts bypassed the reticular formation, which was largely relegated to automatic functions. In mammals, the tectum in turn has been relegated to minor status with the emergence of very fast pathways linking the cerebral cortex with the peripheral sensory and motor apparatus.

In the human brain, the reticular formation continues to be of importance in automatic and reflex activities, and it has retained its linkages to the limbic system.

Organization

The term reticular formation refers only to the polysynaptic network in the brainstem, although the network continues rostrally into the thalamus and hypothalamus, and caudally into the propriospinal network of the spinal cord.

The ground plan is shown in Figure 24.1A. In the midline, the median reticular formation comprises a series of raphe nuclei (pron. ‘raffay’ and derived from the Greek word for seam). The raphe nuclei are the major source of serotonergic projections throughout the neuraxis (see next section).

Figure 24.1 Reticular formation (RF). (A) Subdivisions. (B) Aminergic and cholinergic cell groups.

Next to this is the paramedian reticular formation. This part of the network contains magnocellular neurons throughout; in the lower pons and upper medulla, some gigantocellular neurons also appear, before the network blends with the central reticular nucleus of the medulla oblongata.

Outermost is the lateral, parvocellular (small-celled) reticular formation. Parvocellular dendrites are long and they branch at regular intervals. They have a predominantly transverse orientation, and their interstices are penetrated by long pathways running to the thalamus. The lateral network is mainly afferent in nature. It receives fibers from all of the sensory pathways, including the special senses:

• Olfactory fibers are received through the medial forebrain bundle, which passes alongside the hypothalamus.

• Visual pathway fibers are received from the superior colliculus.

• Auditory pathway fibers are received from the superior olivary nucleus.

• Vestibular fibers are received from the medial vestibular nucleus.

• Somatic sensory fibers are received from the spinoreticular tracts and from the spinal and principal (pontine) nuclei of the trigeminal nerve.

Most parvocellular axons ramify extensively among the dendrites of the paramedian reticular formation. However, some synapse within the nuclei of cranial nerves and act as pattern generators (see later).

The paramedian reticular formation is a predominantly efferent system. The axons are relatively long. Some ascend to synapse in the midbrain reticular formation or in the thalamus. Others have both ascending and descending branches contributing to the polysynaptic network. The magnocellular component receives corticoreticular fibers from the premotor cortex and gives rise to the pontine and medullary reticulospinal tracts.

Aminergic neurons of the brainstem

Embedded in the reticular formation are sets of aminergic neurons (Figure 24.1B). They include one set producing serotonin (5-hydroxytryptamine) and three sets producing catecholamines, as listed in Table 24.1.

• The serotonergic neurons have the largest territorial distribution of any set of CNS neurons. In general terms, those of the midbrain project rostrally into the cerebral hemispheres; those of the pons ramify in the brainstem and cerebellum; and those of the medulla supply the spinal cord (Figure 24.2). All parts of the CNS gray matter are permeated by serotonin-secreting axonal varicosities. Clinically, enhancement of serotonin activity is part of the treatment for a prevalent condition known as major depression (Ch. 26).

• The dopaminergic neurons of the midbrain fall into two groups. At the junction of tegmentum and crus are those of the substantia nigra, which will be considered in Chapter 33. Medial to these, dopaminergic neurons in the ventral tegmental nuclei (Figure 24.3) project mesocortical fibers to the frontal lobe and mesolimbic fibers to the nucleus accumbens in particular (Ch. 34).

• The noradrenergic neurons are only marginally less prodigious than the serotonergic ones. About 90% of the somas are pooled in the cerulean nucleus (locus ceruleus), a ‘violet spot’ in the floor of the fourth ventricle at the upper end of the pons (Figure 24.4). Neurons of the cerulean nucleus project in all directions, as indicated in Figure 24.5.

• Epinephrine-secreting neurons are relatively scarce and are confined to the medulla oblongata. Some project rostrally to the hypothalamus, others project caudally to synapse upon preganglionic sympathetic neurons in the spinal cord.

Table 24.1 Aminergic neurons of the reticular formation

Transmitter	Location
Serotonin	Raphe nuclei of midbrain, pons, medulla
Dopamine	Tegmentum of midbrain
Norepinephrine	Midbrain, pons, medulla
Epinephrine	Medulla

Figure 24.2 Serotonergic projections from the brainstem midline (raphe).

Figure 24.3 Dopaminergic projections from the midbrain.

Figure 24.5 Noradrenergic projections from the pons and medulla oblongata.

Figure 24.4 Part of a transverse section through the upper part of the pons, showing elements of the reticular formation.

In the cerebral cortex, the ionic and electrical effects of aminergic neuronal activity are quite variable. First, more than one kind of postsynaptic receptor exists for each of the amines. Second, some aminergic neurons liberate a peptide substance also, capable of modulating the transmitter action – usually by prolonging it. Third, the larger cortical neurons receive many thousands of excitatory and inhibitory synapses from local circuit neurons, and they have numerous different receptors. Activation of a single kind of aminergic receptor may have a large or small effect depending on the existing excitatory state.

Although our understanding of the physiology and pharmacology of the monoamines is far from complete, no-one disputes their relevance to a wide range of behavioral functions.

Functional Anatomy

The range of functions served by different parts of the reticular formation is indicated in Table 24.2.

Table 24.2 Elements of the reticular formation and their perceived functions

Element	Function
Premotor cranial nerve nuclei	Patterned cranial nerve activities
Pontine locomotor center	Pattern generation
Magnocellular nuclei	Posture, locomotion
Salivatory nuclei	Salivary secretion, lacrimation
Pontine micturition center	Bladder control
Medial parabrachial nucleus	Respiratory rhythm
Central reticular nucleus of medulla oblongata	Vital centers (circulation, respiration)
Lateral medullary nucleus	Conveys somatic and visceral information to the cerebellum
Ascending reticular activating system (ARAS)	Arousal
Aminergic neurons	Sleeping and waking, attention and mood, sensory modulation, blood pressure control