1.2 Organization of the Nervous System

Neuroscience across species: neural nets, ganglia and centralized brains

All multicellular organisms with the exception of sponges have neurons and nervous systems, albeit varying in structure and complexity. Large differences are observed between animals with or without a backbone (vertebrates vs. invertebrates). Two general principles in nervous system organization across the animal kingdom include: neural nets and ganglia (Figure 1.13).

Figure 1.13 Diversity of the nervous system organization Image credit: OpenStax Biology 2e, 35.1: Neurons and glial cells; credit Human, modification of work by NIH.

Cnidaria (includes hydra, corals, jellyfish, and anemones) have neural nets. These are the simplest—and, considered evolutionarily, the oldest—form of nervous system organization. We can describe them as mesh-like systems of separate, yet interconnected neurons (not clustered into nerves or centralized). Nerve nets can be diffuse or can be connected to each other via long nerve cords, as in the case of flatworms. Nerves are defined as bundles of fibers (axons) that transmit information.

Nerve cords can be arranged in a ladder-like conformation and connected to ganglia. Ganglia are structures that contain collections of neuronal cell bodies and are found in animals more complex than Cnidaria, such as flatworms. Many invertebrates actually have more than one ganglia, each with specific functions, such as control of different muscles or, in the case of earthworms, different body segments. Often there is a cerebral ganglion which serves a more coordinative role. In contrast, vertebrates have a spinal cord encased in vertebral bones. The spinal cord runs along their back and most of the nervous system that is important for complex behavior is centralized and concentrated in a brain located in the head.

Animal symmetry

Humans and many other animals, including other vertebrates and some invertebrates, have bilateral body plans meaning that the left and right sides of the body are mirror images of each other. Other animals like jellyfish and sea stars are arranged centrally around a gastrointestinal core. This is called radial symmetry. While bilateral organisms often have one nerve cord and centralized ganglia or a brain that controls both sides of the body, radially symmetrical organisms lack a central brain and have radial nerves (sea star) or nerve nets (hydra) (Figure 1.13 and Figure 1.14).

Figure 1.14 Bilateral vs radial symmetry

Centralization and cephalization

Nervous systems of animals with bilateral symmetry exhibit centralization and cephalization. Centralization refers to a nervous system organization where neurons are consolidated into specific areas of integration rather than just being randomly arranged throughout the body. Cephalization refers to the concentration of the nervous system at the anterior part of the body or the head. Flatworms, considered one of the simplest organisms with bilateral symmetry, exhibit both centralization and cephalization, having ganglia at the anterior end of their body (Figure 1.13). All vertebrate nervous systems contain a central nervous system (CNS) (brain and spinal cord) and a peripheral nervous system (PNS) (peripheral motor and sensory nerves).

The basic organization and structure of the vertebrate nervous system

The human nervous system shares the same basic plan found in all vertebrates and we humans are not unique in our brain organization. The human brain is a vertebrate brain and basically a large primate brain. Our nervous system can be divided according to anatomical structures and/or functional regions. This section will introduce the CNS and PNS and highlight some important features of the two systems (Figure 1.15).

Figure 1.15 Vertebrate nervous system organization

CNS and PNS

The human nervous system, like other vertebrate nervous systems, is organized into the central nervous system (CNS), which is composed of the brain and spinal cord, and peripheral nervous system (PNS), which includes all nerves and ganglia outside of the spinal cord and brain. Groups of neurons are segregated into nuclei in the CNS and ganglia in the PNS. Axon bundles are called nerves in the PNS and tracts in the CNS (Figure 1.16). Ascending tracts take information to the brain and descending tracts away from the brain. Vertebrate nervous systems are highly centralized with higher neural functions like memory, learning, perception and movement carried out within the brain. The spinal cord sends sensory information to the brain and conveys motor commands from the brain to the entire body. In addition, there are circuits found in the spinal cord that perform local processing and allow for simple behaviors such as reflexes to occur without the direct involvement of the brain. The spinal cord also contains central pattern generator circuitry that allows for rhythmic behavior such as walking (see Chapter 10 Motor Control). The PNS is responsible for carrying messages between the CNS and all body parts, including muscles, organs, and the body periphery in general. A more detailed discussion of the CNS and PNS can be found below.

Figure 1.16 Nervous system basics

Gray and white matter

The nervous system is made up of gray and white matter (Figure 1.16). This terminology refers to gross histological distinctions. Gray matter, named for its pinkish-gray color, has a high concentration of neuronal cell bodies, dendrites and axons that are not myelinated. White matter is composed of axon fibers covered in myelin, giving it its whitish color. Gray matter is found in the outermost layer of the brain and centrally within the spinal cord. White matter is in the deeper tissues of the brain and surrounds the gray matter in the spinal cord.

Meninges

The CNS is covered in bone. A skull encases the brain while the spinal cord is housed in a collection of 33 small bones called vertebrae. Between the bones and the nervous tissue of the CNS, there are layers of cushiony tissue called the meninges. The three layers of the meninges are dura mater, arachnoid mater and pia mater. The dura mater layer is found directly against the skull and vertebrae, and is the thickest layer of the three meninges (Figure 1.17).

Figure 1.17 The meninges

Ventricles

Ventricles are interconnected cavities or open spaces located in the brain and spinal cord that contain cerebrospinal fluid (CSF). They serve two main functions: 1) to cushion the brain and 2) to allow exchange of materials between the brain and blood vessels. CSF is produced by the choroid plexus, a tissue rich in blood vessels found in the lining of the ventricles. It is a clear liquid, essentially filtered blood. Spinal taps are medical procedures to remove a small amount of CSF to test for medical conditions or infections in the brain. The ventricular system is composed of 4 ventricles and an aqueduct (Figure 1.18). Think of the ventricles as being similar to the great lakes: independent bodies of water but connected by rivers (aqueduct). The 2 large lateral ventricles in each cerebral hemisphere (left and right) connect to a third ventricle (in the diencephalon) which opens into the cerebral aqueduct (in the midbrain) and a fourth ventricle (in the hindbrain). The fourth ventricle extends to the central canal which is filled with CSF and runs across the spinal cord. CSF fills the ventricular system and circulates over the brain and spinal cord. It flows through the subarachnoid space and exits through the arachnoid villi into venous sinuses, a group of blood channels found throughout the brain. Eventually CSF is reabsorbed into the circulatory system. CSF is also found surrounding the brain below the arachnoid membrane called the subarachnoid space (Figure 1.18).

Figure 1.18 The cerebrospinal fluid (CSF)

Vascular system of the brain

The human brain requires a disproportionate amount of energy in the form of ATP to function properly. ATP production requires oxygen, which is supplied by a constantly circulating blood supply. As a result, the brain has a complex system of blood vessels. Three main arteries (anterior, middle and posterior cerebral) are the main suppliers of blood to the cerebral hemispheres. The anterior and middle arteries arise from the carotid arteries on the left and right sides of the neck. The vertebral arteries run through the spinal column in the neck to provide blood to the brain and spinal cord, and give rise to the basilar artery. There are many vessels and capillaries that branch off from the main arteries delivering nutrients and removing waste (Figure 1.19). The endothelial cells that form the walls of brain capillaries are extremely well connected to each other and form the blood-brain barrier (BBB), which we discussed in the previous section. This serves as a layer of protection not found in other organs that prevents the flow of some substances like toxins or drugs and also protects against infections.

Figure 1.19 Brain vasculature Image credit: Torso has labels added, original by Laboratoires Servier - Smart Servier website: Cardiovascular system, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=127936249

Neural circuits

Neurons do not function independently. Rather, neurons are organized into simple or complex functional arrangements called neural circuits. A neural circuit represents a group of neurons connected by synapses that process specific types of information. Circuits range from very simple to exceptionally complex. One of the big challenges in modern neuroscience is to understand the complex ways in which circuits are built and function. Large scientific efforts are focusing on the enormous task of building detailed maps of brain circuitry. In this section, we will explore the basic building blocks and functionality of a simple circuit and introduce you to the research focused on more complex circuitry.

Basic building blocks of neural circuits

While neural circuits vary in function, anatomic arrangements and complexity, we can establish some basic principles. As introduced in 1.1 Building a Nervous System, afferent (sensory) neurons carry information about the inside of the body and external environment to the brain or spinal cord while efferent (motor) neurons carry information from other neurons away from the brain/spinal cord or specific circuit. Interneurons serve as a bridge between other neurons and are found in the CNS. They are local circuit neurons that make intra-circuit connections and can act as regulators or adjustors to the circuit (Figure 1.20).

Figure 1.20 Afferent, efferent and interneurons

Simple human circuit example

A reflex arc is a simple neuronal circuit that controls a reflex beginning with a sensory neuron at a receptor (for example, pain receptors on a finger) and ending with a motor neuron at an effector (like a muscle). Reflex arcs are important for the generation of fast reactions to external stimuli such as accidentally placing your finger into an open flame or on a hot surface. Reflex actions are essential to the survival of organisms. To prevent bodily damage, a movement or response that is almost instantaneous and involuntary is required.

In a reflex arc, the sensory neurons do not pass information directly to the brain but rather information travels to the spinal cord, which, in turn, causes direct activation of spinal motor neurons. These neurons can then activate muscles that allow your hand to move away from the hot surface. Of course, information about such an event must eventually get to the brain to allow learning and future avoidance. Another example of a simple human circuit is the knee-jerk reflex (Figure 1.21), which allows for involuntary movement of the leg in response to a sharp tap to the tendon below the knee cap. The knee-jerk reflex is an example of a reflex pathway that is both excitatory and inhibitory (once the extensor muscle on the thigh contracts, the flexor muscle on the back of the thigh must relax). Stimulation of stretch receptors via the tap leads to afferent sensory neuron(s) activation, which in turn synapses either onto interneurons or directly onto efferent motor neurons that cause contraction of the extensor muscles. The interneuron serves to inhibit the motor neurons that connect to flexor muscles which keeps the flexor muscle relaxed. This combined action leads to leg extension (Figure 1.21). This reflex prevents knee collapse in the event of a sudden leg bend.

Figure 1.21 Simple circuit example

Mapping complex brain circuits

A major goal in neuroscience is the mapping of complex neural circuits in the human brain. Because the human brain is exceptionally complex with its 86 billion neurons, each communicating with hundreds or even thousands of other neurons, this is an extremely difficult endeavor. Scientists hope to one day complete the task of mapping the human brain connectome (a comprehensive map of neuronal connections in the brain akin to a wiring diagram). In the meantime, neuroscientists have been using simple animals like worms and flies to develop wiring maps that can provide clues to how brains work in general. Presently, two comprehensive wiring diagrams have been published: the roundworm (C. elegans) nervous system which has a very small number of neurons (302 neurons and 7000 connections) and most recently the entire brain of a fruit fly larva (D. melanogaster), made up of 3016 neurons and 548,000 connections.

There are several large, international, ongoing human mapping projects. These include the Human Connectome Project started in 2009 whose aim was to build a healthy human brain connectome and develop connectomes related to human disease. Building onto the Human Connectome Project, the BRAIN Initiative was started in 2013 with the aim of producing a dynamic picture of the brain which would map individual brain cells and the circuits that they take part in both time and space. The goal with such large projects and initiatives is to provide a deeper understanding of brain function and as a result develop new treatments for brain disorders. In 2021, the BRAIN initiative unveiled a detailed atlas of a small brain region, the mammalian primary motor cortex, derived from studies in mice, monkeys and humans.