THE RETICULAR SYSTEM, SLEEP AND AROUSAL

Strong stimulation at a point on the body will evoke a short-latency response localized to the relevant somatotopic area of the cerebral cortex. This is followed by a longer-latency, more generalized response which arrives at the cortex via the slower, less specific polysynaptic relays of the reticular formations (RF). Like the descending pathways from the RF, which provide background tone and postural set against which specific actions are carried out, the ascending projections provide the background arousal and activity, required for sensory processing, cognition and consciousness. Inputs from the RF reach the cerebral cortex either directly, or via relays in the non-specific intralaminar, reticular & mid-line thalamic nuclei. Lesions in the tegmental areas, or other pathways, through which specific, somatotopically organized inputs project to the cerebral cortex, cause loss of specific sensory perceptions, but not of consciousness or arousal. However, lesion of the medial pathways from the mid-brain RF, result in coma: irreversible loss of consciousness, and of arousal in response to sensory stimuli. Impaired functioning of this system may lead to stupor: reduced awareness of the surroundings and responsiveness only to strong stimuli. Because of the presence in the RF of long, unmyelinated axons, and many synapses, it is particularly susceptible to general anaesthetics. These substances all are highly lipid soluble, penetrate the blood-brain barrier readily and reduce excitability, particularly of unmyelinated axonal membranes. The reticular areas contributing to background arousal, and maintenance of consciousness, together constitute the Ascending Reticular Activating System (ARAS). The ARAS excites the generalized cerebral cortex, from which it receives positive feedback excitation for sustaining alertness and awareness. The descending, spinal projections of the ARAS help to maintain background tone in the spinal cord.

Through the day, periods of alertness give way to inattention, somnolence and sleep in repeating and quite predictable sequences. Levels of consciousness can be graded clinically on the basis of responsiveness to questioning and to stimuli of differing intensity. More rigorous characterization of the global, background state of cerebral cortical activity however, can be obtained using the electroencephalogram (EEG). The standard EEG is a pattern of oscillatory electrical activity, recorded by placing electrodes at standard locations on the surface of the scalp. Recording may be differential - between pairs of electrodes in a systematic sequence, or monopolar - between each electrode and an indifferent reference (linked ear-lobes; shoulder; all head electrodes linked through a set resistance). The activity recorded arises as a result of the summed synaptic currents in extensive arrays of pyramidal cells. These cells are aligned at right angles to the cortical surface and produce current sinks and/or sources, in response either to excitatory synaptic input onto dendrites in the superficial layers, or to inhibitory synaptic input onto the more deeply lying cell bodies. The synchronicity and periodicity of these inputs depend on the nature of the activity in thalamo-cortical and reticulo-cortical, and thalamo-reticular circuits, and determine the amplitude and frequency of the waveforms in the EEG.

The EEG has been a most useful tool in the study of sleep. Sleep is a periodically occurring (circadian), spontaneously reversible reduction in awareness of external events, from which the sleeper can be aroused by strong external stimuli. Sleep occupies about one third of our adult lives; deprivation leads to increasingly inexorable desire to sleep, poor co-ordination, inattentiveness, reduced learning ability and, by some reports, ultimately death. Despite this, the fundamental reason why we need to sleep is still not clear. The circadian onset is determined by an internal clock in the suprachiasmatic nucleus, with an intrinsic cycle of about 25 hrs. The clock becomes entrained to the ambient (24 hr) cycle of day/night and daily activities. However, in sleep deprived animals, substances (delta sleep inducing peptide, DSIP; muramyl peptides) accumulate in blood and CSF, and when injected into well-rested animals, can induce sleep. The process of sleep is not merely the withdrawal of ARAS activity. Onset, continuation and termination of sleep are highly structured activities, which occur under active control.

The onset of sleep involves the gradual reduction of EEG beta activity, and increased dominance of alpha, and irregular EEG activity (Stage 1 sleep). Muscle tone falls, and con-sciousness wanes, although passing awareness of external events still persists.

Activity in the locus coeruleus (LC) falls progressively as sleep deepens; this may release normally inhibited cholinergic cells of the TGF which may be responsible for the reduced tonus and PGO spikes seen during REM. In the upper pons is a "wakefulness" centre, which, after mid-pontine section, may induce perpetual wakefulness. This could be the LC cells. Slightly lower section allows normal sleep wake cycles - presumably by including cells which periodically turn off the "wakefulness" centre. These sleep-inducing cells may include the serotonergic raphe nuclei, which are excited by sleep inducing peptides. Destruction of these cells leads (temporarily) to continuous wakefulness: they serve normally to suppress inflow of sensory stimuli and to inhibit phasic REM activity.

Disruptions of sleep include insomnia, narcolepsy (sudden, inexorable sleep onset), parasomnias (somnoambulism, bed-wetting, sleep apnea etc.). Barbiturates may help insomnia at first, then with prolonged use, disrupt REM sleep. Accumulating metabolites of the barbiturates also disrupt daytime motor coordination. Benzodiazepines are better - they affect SWS more than REM sleep, and do not affect day-time motor coordination.

Read Ganong: Review of Medical Physiology, Chapter 11.

Somjen: Neurophysiology - the essentials, Chapter 19