Circuits of the Central Nervous System

Neural circuits process sensory information, generate motor output, and create spontaneous activity

A neuron never works alone. Even in the most primitive nervous systems, all neurons participate in synaptically interconnected networks called circuits. In some hydrozoans (small jellyfish), the major neurons lack specialization and are multifunctional. They serve simultaneously as photodetectors, pattern generators for swimming rhythms, and motor neurons. Groups of these cells are repetitively interconnected by two-way electrical synapses into simple ring-like arrangements, and these networks coordinate the rhythmic contraction of the animal's muscles during swimming. This simple neural network also has the flexibility to command defensive changes in swimming patterns when a shadow passes over the animal. Thus, neuronal circuits have profound advantages over unconnected neurons.

In more complex animals, each neuron within a circuit may have very specialized properties. By the interconnection of various specialized neurons, even a simple neuronal circuit may accomplish astonishingly intricate functions. Some neural circuits may be primarily sensory (e.g., the retina) or motor (e.g., the ventral horns of the spinal cord). Many circuits combine features of both, with some neurons dedicated to providing and processing sensory input, others to commanding motor output, and many neurons (perhaps most) doing both. Neural circuits may also generate their own intrinsic signals, with no need for any sensory or central input to activate them. The brain does more than just respond reflexively to sensory input, as a moment's introspection will amply demonstrate. Some neural functions—such as walking, running, breathing, chewing, talking, and piano playing—require precise timing, with coordination of rhythmic temporal patterns across hundreds of outputs. These basic rhythms may be generated by neurons and neural circuits called pacemakers because of their clock-like capabilities. The patterns and rhythms generated by a pacemaking circuit can always be modulated—stopped, started, or altered—by input from sensory or central pathways. Neuronal circuits that produce rhythmic motor output are sometimes called central pattern generators; we discuss these in a section below.

This chapter introduces the basic principles of neural circuits in the mammalian central nervous system (CNS). We describe a few examples of specific systems in detail to illuminate general principles as well as the diversity of neural solutions to life's complex problems. However, this topic is enormous, and we have necessarily been selective and somewhat arbitrary in our presentation.

Nervous systems have several levels of organization

The function of a nervous system is to generate adaptive behaviors. Because different species face unique problems, we expect brains to differ in their organization and mechanisms. Nevertheless, certain principles apply to most nervous systems. It is useful to define various levels of organization. N16-1 We can analyze a complex behavior —reading the words on this page—in a simple way, with progressively finer detail, down to the level of ion channels, receptors, messengers, and the genes that control them. At the highest level, we recognize neural subsystems and pathways (see Chapter 10 ), which in this case include the sensory input from the retina (see Chapter 15 ) leading to the visual cortex, the central processing regions that make sense of the visual information and the motor systems that coordinate movement of the eyes and head. Many of these systems can be recognized in the gross anatomy of the brain. Each specific brain region is extensively interconnected with other regions that serve different primary functions. These regions tend to have profuse connections that send information in both directions along most sensory/central motor pathways. The advantages of this complexity are obvious; while you are interpreting visual information, for example, it can be very useful simultaneously to analyze sound and to know where your eyes are pointing and how your body is oriented.

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Levels of Organization of the Nervous System

The systems of the brain can be more deeply understood by studying their organization at the cellular level. Within a local brain region, the arrangement of neurons and their synaptic connections is called a local circuit. A local circuit typically includes the set of inputs, outputs, and all the interconnected neurons that are essential to functions of the local brain region. Many regions of the brain are composed of a large number of stereotyped local circuits, almost modular in their interchangeability, that are themselves interconnected. Within the local circuits are finer arrangements of neurons and synapses sometimes called microcircuits. Microcircuits may be repeated numerous times within a local circuit, and they determine the transformations of information that occur within small areas of dendrites and the collection of synapses impinging on them. At even finer resolution, neural systems can be understood by the properties of their individual neurons (see Chapter 12 ), synapses, membranes, molecules (e.g., neurotransmitters and neuromodulators), and ions as well as the genes that encode and control the system's molecular biology.

Most local circuits have three elements: input axons, interneurons, and projection (output) neurons

One of the most fascinating things about the nervous system is the wide array of different local circuits that have evolved for different behavioral functions. Despite this diversity, we can define a few general components of local circuits, which we illustrate with two examples from very different parts of the CNS: the ventral horn of the spinal cord and the cerebral neocortex. Some of the functions of these circuits are described in subsequent sections; here, we examine their cellular anatomy.

All local circuits have some form of input, which is usually a set of axons that originate elsewhere and terminate in synapses within the local circuit. A major input to the spinal cord ( Fig. 16-1 ) is the afferent sensory axons in the dorsal roots. These axons carry information from somatic sensory receptors in the skin, connective tissue, and muscles (see pp. 383–389 ). However, local circuits in the spinal cord also have many other sources of input, including descending input from the brain and input from the spinal cord itself, both from the contralateral side and from spinal segments above and below. Input to the local circuits of the neocortex ( Fig. 16-2 ) is also easily identified; relay neurons of the thalamus send axons into particular layers of the cortex to bring a range of information about sensation, motor systems, and the body's internal state. By far, the most numerous type of input to the local circuits of the neocortex comes from the neocortex itself—from adjacent local circuits, distant areas of cortex, and the contralateral hemisphere. These two systems illustrate a basic principle: local circuits receive multiple types of input.

Output is usually achieved with a subset of cells known as projection neurons, or principal neurons, which send axons to one or more targets. The most obvious spinal output comes from the α motor neurons, which send their axons out through the ventral roots to innervate skeletal muscle fibers. Output axons from the neocortex come mainly from large pyramidal neurons in layer V, which innervate many targets in the brainstem, spinal cord, and other structures, as well as from neurons in layer VI, which make their synapses back onto the cells of the thalamus. However, as was true with inputs, most local circuits have multiple types of outputs. Thus, spinal neurons innervate other regions of the spinal cord and the brain, whereas neocortical circuits make most of their connections to other neocortical circuits.

Rare, indeed, is the neural circuit that has only input and output cells. Local processing is achieved by additional neurons whose axonal connections remain within the local circuit. These neurons are usually called interneurons or intrinsic neurons. Interneurons vary widely in structure and function, and a single local circuit may have many different types. Both the spinal cord and neocortex have excitatory and inhibitory interneurons, interneurons that make very specific or widely divergent connections, and interneurons that either receive direct contact from input axons or process only information from other interneurons. In many parts of the brain, interneurons vastly outnumber output neurons. To take an extreme example, the cerebellum has ~10 ¹¹ granule cells—a type of excitatory interneuron—which is more than the total number of all other types of neurons in the entire brain!

The “principles” of local circuits outlined here have many variations. For example, a projection cell may have some of the characteristics of an interneuron, as when a branch of its output axon stays within the local circuit and makes synaptic connections. This branching is the case for the projection cells of both the neocortex (pyramidal cells) and the spinal cord (α motor neurons). On the other hand, some interneurons may entirely lack an axon and instead make their local synaptic connections through very short neurites or even dendrites. In some rare cases, the source of the input to a local circuit may not be purely synaptic but chemical (as with CO ₂ -sensitive neurons in the medulla; see p. 714 ) or physical (as with temperature-sensitive neurons in the hypothalamus; see p. 1199 ). Although the main neurons within a generic local circuit are wired in series (see Figs. 16-1 and 16-2 ), local circuits, often in massive numbers, operate in parallel with one another. Furthermore, these circuits usually demonstrate a tremendous amount of crosstalk; information from each circuit is shared mutually, and each circuit continually influences neighboring circuits. Indeed, one of the things that makes analysis of local neural circuits so exceptionally difficult is that they operate in highly interactive, simultaneously interdependent, and expansive networks.

Passive stretching of a skeletal muscle causes a reflexive contraction of that same muscle and relaxation of the antagonist muscles

Reflexes are among the most basic of neural functions and involve some of the simplest neuronal circuits. A motor reflex is a rapid, stereotyped motor response to a particular sensory stimulus. Although the existence of reflexes had been long appreciated, it was Sir Charles Sherrington N10-2 who, beginning in the 1890s, first defined the anatomical and physiological bases for some simple spinal reflexes. So meticulous were Sherrington's observations of reflexes and their timing that they offered him compelling evidence for the existence of synapses, a term he originated.

Reflexes are essential, if rudimentary, elements of behavior. Because of their relative simplicity, more than a century of research has taught us a lot about their biological basis. However, reflexes are also important for understanding more complex behaviors. Intricate behaviors may sometimes be built up from sequences of simple reflexive responses. In addition, neural circuits that generate reflexes almost always mediate or participate in much more complex behaviors. Here we examine a relatively well understood example of reflex-mediating circuitry.

The CNS commands the body to move about by activating motor neurons, which excite skeletal muscles (Sherrington called motor neurons the final common path). Motor neurons receive synaptic input from many sources within the brain and spinal cord, and the output of large numbers of motor neurons must be closely coordinated to achieve even uncomplicated actions such as walking. However, in some circumstances, motor neurons can be commanded directly by a simple sensory stimulus—muscle stretch—with only the minimum of neural machinery intervening between the sensory cell and motor neuron: one synapse. Understanding of this simplest of reflexes, the stretch reflex or myotatic reflex, first requires knowledge of some anatomy.

Each motor neuron, with its soma in the spinal cord or brainstem, commands a group of skeletal muscle cells; a single motor neuron and the muscle cells that it synapses on are collectively called a motor unit (see pp. 241–242 ). Each muscle cell belongs to only one motor unit. The size of motor units varies dramatically and depends on muscle function. In small muscles that generate finely controlled movements, such as the extraocular muscles of the eye, motor units tend to be small and may contain just a few muscle fibers. Large muscles that generate strong forces, such as the gastrocnemius muscle of the leg, tend to have large motor units with as many as several thousand muscle fibers. There are two types of motor neurons (see Table 12-1 ): α motor neurons innervate the main force-generating muscle fibers (the extrafusal fibers), whereas γ motor neurons innervate only the fibers of the muscle spindles. The group of all motor neurons innervating a single muscle is called a motor neuron pool (see pp. 241–242 ).

When a skeletal muscle is abruptly stretched, a rapid, reflexive contraction of the same muscle often occurs. The contraction increases muscle tension and opposes the stretch. This stretch reflex is particularly strong in physiological extensor muscles—those that resist gravity—and it is sometimes called the myotatic reflex because it is specific for the same muscle that is stretched. The most familiar version is the knee jerk, which is elicited by a light tap on the patellar tendon. The tap deflects the tendon, which then pulls on and briefly stretches the quadriceps femoris muscle. A reflexive contraction of the quadriceps quickly follows ( Fig. 16-3 ). Stretch reflexes are also easily demonstrated in the biceps of the arm and the muscles that close the jaw. Sherrington showed that the stretch reflex depends on the nervous system and requires sensory feedback from the muscle. For example, cutting the dorsal (sensory) roots to the lumbar spinal cord abolishes the stretch reflex in the quadriceps muscle. The basic circuit for the stretch reflex begins with the primary sensory axons from the muscle spindles (see p. 388 ) in the muscle itself. Increasing the length of the muscle stimulates the spindle afferents, particularly the large group Ia axons from the primary sensory endings. In the spinal cord, these group Ia sensory axons terminate monosynaptically onto the α motor neurons that innervate the same (i.e., the homonymous) muscle from which the group Ia axons originated. Thus, stretching a muscle causes rapid feedback excitation of the same muscle through the minimum possible circuit: one sensory neuron, one central synapse, and one motor neuron ( Box 16-1 ).

Monosynaptic connections account for much of the rapid component of the stretch reflex, but they are only the beginning of the story. At the same time the stretched muscle is being stimulated to contract, parallel circuits are inhibiting the α motor neurons of its antagonist muscles (i.e., those muscles that move a joint in the opposite direction). Thus, as the knee-jerk reflex causes contraction of the quadriceps muscle, it simultaneously causes relaxation of its antagonists, including the semitendinosus muscle (see Fig. 16-3 ). To achieve inhibition, branches of the group Ia sensory axons excite specific interneurons that inhibit the α motor neurons of the antagonists. This reciprocal innervation increases the effectiveness of the stretch reflex by minimizing the antagonistic forces of the antagonist muscles.

Force applied to the Golgi tendon organ regulates muscle contractile strength

Skeletal muscle contains another mechanosensory transducer in addition to the stretch receptor: the Golgi tendon organ (see p. 388 ). Tendon organs are aligned in series with the muscle; they are exquisitely sensitive to the tension within a tendon and thus respond to the force generated by the muscle rather than to muscle length. Tendon organs may respond during passive muscle stretch, but they are stimulated particularly well during active contractions of a muscle. The group Ib sensory axons of the tendon organs excite both excitatory and inhibitory interneurons within the spinal cord ( Fig. 16-4 ). In some cases, this interneuron circuitry inhibits the muscle in which tension has increased and excites the antagonistic muscle; therefore, activity in the tendon organs can yield effects that are almost the opposite of the stretch reflex. Under other circumstances, particularly during rapid movements such as locomotion, sensory input from Golgi tendon organs actually excites the motor neurons activating the same muscle. The reflex effects of Golgi tendon organ activity vary because the interneurons receiving input from Ib axons also receive input from other sensory endings in the muscle and skin, and from axons descending from the brain. In general, reflexes mediated by the Golgi tendon organs serve to control the force within muscles and the stability of particular joints.

Noxious stimuli can evoke complex reflexive movements

Sensations from the skin and connective tissue can also evoke strong spinal reflexes. Imagine walking on a beach and stepping on a sharp piece of shell. Your response is swift and coordinated and does not require thoughtful reflection: you rapidly withdraw the wounded foot by activating the leg flexors and inhibiting the extensors. To keep from falling, you also extend your opposite leg by activating its extensors and inhibiting its flexors ( Fig. 16-5 ). This response is an example of a flexion-withdrawal reflex. The original stimulus for the reflex came from fast pain afferent neurons in the skin, primarily the group Aδ axons.

This bilateral flexor reflex response is coordinated by sets of inhibitory and excitatory interneurons within the spinal gray matter. Note that this coordination requires circuitry not only on the side of the cord ipsilateral to the wounded side but also on the contralateral side. That is, while you withdraw the foot that hurts, you must also extend the opposite leg to support your body weight. Flexor reflexes can be activated by most of the various sensory afferents that detect noxious stimuli. Motor output spreads widely up and down the spinal cord, as it must to orchestrate so much of the body's musculature into an effective response. A remarkable feature of flexor reflexes is their specificity. Touching a hot surface, for example, elicits reflexive withdrawal of the hand in the direction opposite the side of the stimulus, and the strength of the reflex is related to the intensity of the stimulus. Unlike simple stretch reflexes, flexor reflexes coordinate the movement of entire limbs and even pairs of limbs. Such coordination requires precise and widespread wiring of the spinal interneurons.