46: The Modulatory Functions of the Brain Stem

Introduction

• Ascending Monoaminergic and Cholinergic Projections from the Brain Stem Maintain Arousal

• Monoaminergic and Cholinergic Neurons Share Many Properties and Functions

  • Many Monoaminergic and Cholinergic Neurons Are Linked to the Sleep-Wake Cycle

  • Monoaminergic and Cholinergic Neurons Maintain Arousal by Modulating Neurons in the Thalamus and Cortex

• Monoamines Regulate Many Brain Functions Other Than Arousal

  • Cognitive Performance Is Optimized by Ascending Projections from Monoaminergic Neurons

  • Monoamines Are Involved in Autonomic Regulation and Breathing

  • Pain and Anti-nociceptive Pathways Are Modulated by Monoamines

  • Monoamines Facilitate Motor Activity

• An Overall View

• Postscript: Evaluation of the Comatose Patient

As we learned in the previous chapter, the brain stem can respond independently to the environment with stereotypic actions. We have also seen, in discussing the sensory and motor systems, that the brain stem is the conduit for all ascending and descending pathways between the forebrain, spinal cord, and peripheral nervous system. In this chapter we examine still a third role of the brain stem, as the modulatory center that orchestrates the activity of the rest of the central nervous system, ensuring that its activity is optimized.

This modulatory function is mediated by several small groups of neurons in the brain stem. These neurons project widely, using as neurotransmitters acetylcholine and the monoamines (norepinephrine, epinephrine, serotonin, dopamine, and histamine). Many of the monoaminergic groups modify pain and help regulate the autonomic nervous system to maintain internal homeostasis. Some are essential for controlling the level of behavioral arousal; and together they influence attention, mood, and memory. Because they are involved in the pathophysiology of many human diseases and are targets of many commonly used drugs, these monoaminergic and cholinergic neurons are also important for clinical care.

Behaviors we regard as uniquely human, such as memory, language, and compassion, depend heavily on modulation of forebrain function by the ascending cholinergic and monoaminergic systems. This dependence is seen clinically in the links between Alzheimer's disease and the acetylcholine system, schizophrenia and the dopaminergic system, and alleviation of depression with drugs that affect serotonergic and noradrenergic synapses. Thus, although the brain stem is phylogenetically primitive, the modulatory systems that project from this region enable and modulate many of the higher-order behaviors that we regard as most human.

Ascending Monoaminergic and Cholinergic Projections from the Brain Stem Maintain Arousal

Some neurons in the brain stem that project to the forebrain control wakefulness and sleep. In the mid-1930s Frederic Bremer found that transection of the cat's brain stem at the midbrain level produced a continuous sleep-like state, whereas transections that separated the medulla from the spinal cord did not (Figure 46–1). These experiments demonstrate that the portion of the brain stem from the midbrain to the medulla keeps the forebrain awake.