Comprehensive Histology of the Human Nervous System

Introduction to the Nervous System and the CNS

The Central Nervous System (CNS) consists primarily of the brain and the spinal cord. It is composed of functional units called neurons, their neuronal processes, various supporting cells known as glial cells (or neuroglia), and a network of blood vessels. Structurally, the CNS is invested with protective layers called meninges and is suspended in cerebrospinal fluid (CSF), which serves as a cushioning medium. The CSF is produced by specialized structures known as the choroid plexus.

All parts of the CNS are differentiated into grey matter and white matter based on their cellular components. Grey matter contains the majority of neuronal cell bodies and their dendritic processes, functioning as the primary site of signal processing. In contrast, white matter consists of axons, which are the long processes responsible for carrying impulses between different areas of the nervous system. The pale appearance of white matter is due to the presence of myelinated axons.

Divisions of the Human Nervous System

The nervous system is broadly divided into the Central Nervous System (CNS) and the Peripheral Nervous System (PNS). The PNS is further subdivided based on the type of control and functions it governs. The Somatic Nervous System manages sensory input and motor output related to voluntary control. The Autonomic Nervous System (ANS), which regulates involuntary physiological processes, is split into the Sympathetic and Parasympathetic divisions.

The Sympathetic and Parasympathetic systems often have antagonistic effects on various organs. For instance, the parasympathetic nerves act to constrict pupils, stimulate salivation, constrict airways, slow the heartbeat, stimulate the activity of the stomach and intestines, stimulate the gallbladder, and contract the bladder. It is also associated with promoting the erection of genitals. Conversely, the sympathetic nerves dilate pupils, inhibit salivation, relax airways, increase the heartbeat, inhibit the activity of the stomach and intestines, stimulate the release of glucose from the liver, inhibit the gallbladder, secrete epinephrine and norepinephrine from the adrenal glands, and relax the bladder. These nerves also promote ejaculation and vaginal contractions. The sympathetic chain is a prominent feature of the sympathetic division located alongside the spinal cord.

Fundamental Cells of the Nervous Tissue

Nervous tissue is comprised of two principal cell types: nerve cells (neurons) and glial cells (neuroglia). Neurons are the primary cells of the nervous tissue and are specialized to conduct electrical impulses. Neuroglia, which are approximately $10$ times more abundant than neurons, provide metabolic and mechanical support, nurture neurons, and protect them. Unlike neurons, neuroglial cells retain the ability to undergo mitosis.

A typical neuron consists of three main parts: a cell body, also known as the perikaryon or soma; a single axon; and multiple dendrites. The size of neurons can vary significantly, ranging from $5-150\,\mu m$ in diameter.

Structure and Ultrastructure of the Neuron Cell Body

The cell body is the central portion of the neuron and is generally polygonal in shape, though its specific shape and size are characteristic of particular regions in the nervous system. It contains the nucleus and the perinuclear cytoplasm. The nucleus is typically large, spherical to ovoid, and centrally located, featuring finely dispersed chromatin and a single, prominent nucleolus. In some neurons, sex chromatin may also be visible.

The cytoplasm of the neuron is rich in organelles to support its high metabolic activity. It contains abundant Rough Endoplasmic Reticulum (RER) and polyribosomes, which aggregate into basophilic clumps known as Nissl bodies or Nissl substance. These are essential for protein synthesis. The Golgi apparatus is well-developed, characteristic of protein-secreting cells. A significant amount of Smooth Endoplasmic Reticulum (SER) is present to facilitate lipid synthesis, detoxification, and calcium storage. Multiple mitochondria are distributed throughout the cell, being most abundant in the axon terminals. The cytoskeleton includes neurofibrils (microtubules and intermediate filaments) that facilitate axonal transport. Lipofuscin granules, which are pigments of "wear and tear," may also be present as the cell ages. Despite having a centriole, mature neurons do not undergo cell division.

Characteristics of Dendrites and Axons

Dendrites are multiple elongated processes that extend from the soma. They are primary sites for receiving stimuli from other neurons or the environment and are characterized by a broad base that tapers as they branch. Some dendrites, such as those in the forebrain cortex, feature spiny projections.

The axon is a single process that can reach lengths of up to $100\,cm$. It originates from a specialized region of the soma called the axon hillock, which is notably devoid of ribosomes. The axon is responsible for conducting impulses away from the soma. The distal portion of the axon undergoes dilatation to form axon terminals, also known as end bulbs, which participate in the formation of synapses. Synapses can be classified by their location: axosomatic (axon to cell body), axoaxonic (axon to axon), and axodendritic (axon to dendrite).

Morphological Classification of Neurons

Neurons are classified morphologically based on the number and arrangement of their processes. Unipolar neurons possess a single process and are quite rare in vertebrates. Bipolar neurons feature a single axon and a single dendrite; they are primarily found in specialized sense organs such as the retina of the eye and the vestibulo-cochlear mechanism of the auditory and visual systems.

Multipolar neurons are the most abundant type and possess one axon and multiple dendrites. Examples include pyramidal cells in the cerebral cortex and Purkinje cells in the cerebellum. Pseudounipolar neurons possess a single process that extends from the cell body and subsequently branches into an axon and a dendrite. These are typically found in the spinal and cranial ganglia as well as sensory ganglia.

Functional Classification of Neurons

Neurons are also categorized by their physiological roles. Sensory (Afferent) neurons receive sensory input and conduct these impulses toward the CNS. Motor (Efferent) neurons conduct impulses from the CNS to effector organs like muscles, glands, and other neurons. Interneurons, found entirely within the CNS, act as interconnectors to establish neuronal circuits between sensory and motor neurons.

Types and Functions of Neuroglia in the CNS

There are four principal types of neuroglia in the CNS, each with specialized functions. Astrocytes are highly branched cells that provide mechanical support and mediate the exchange of metabolites between neurons and the vascular system. They are integral to the blood-brain barrier (BBB) and help repair CNS tissue following damage by forming cellular scar tissue. There are two types: Protoplasmic astrocytes, found in grey matter with short, branching processes, and Fibrous astrocytes, found in white matter with long, slender processes. Their pedicles bind to capillaries and the pia mater to form the glial limitans.

Oligodendrocytes are the CNS equivalent of Schwann cells. They are responsible for the formation of myelin sheaths around axons in the CNS, providing electrical insulation. A single oligodendrocyte can wrap around several axons ($40$ to $50$) and is responsible for forming the nodes of Ranvier.

Microglia represent the monocyte-macrophage system within the CNS. These small, mesoderm-derived cells have phagocytic properties and defense functions, clearing debris and acting as Antigen-Presenting Cells (APC). They have small, elongated nuclei and short, thorny processes. Ependymal cells are low columnar ciliated epithelial cells that line the ventricles of the brain and the central canal of the spinal cord. They facilitate the movement of CSF and participate in the formation of the choroid plexus.

Neuroglia and Connective Tissue of the PNS

In the Peripheral Nervous System, Schwann cells are the primary glial cells. They are the analogues of oligodendrocytes and produce the myelin sheath in the PNS. In myelinated fibers, a single Schwann cell wraps around a single axon to form the sheath and the nodes of Ranvier. In unmyelinated fibers, a single Schwann cell envelopes several axons within simple clefts.

Peripheral nerves are bundles of axons surrounded by layers of connective tissue. The Endoneurium is a layer of loose connective tissue regulating the microenvironment of the nerve fiber. The Perineurium is dense connective tissue that isolates the neural environment, forming the blood-nerve barrier. The Epineurium is the outermost layer of dense collagenous connective tissue, containing thick elastic fibers to prevent damage from overstretching.

Histology of the Brain and Spinal Cord

The cerebrum consists of a grey matter cortex and internal white matter. The cerebral grey matter contains six distinct layers composed of neurons, dendrites, and glial cells. The cerebellum also features grey matter with three specific layers: the outer molecular layer, the central layer of large Purkinje cells (with dendritic trees protruding into the molecular layer), and the inner granule layer.

The spinal cord has a central, H-shaped grey matter region surrounded by peripheral white matter. The H-shape consists of anterior horns and posterior horns, containing large multipolar neurons. The spinal cord's central canal is lined by ependymal cells. Neuropil ($Np$) is the dense network of cytoplasmic processes (axons and dendrites) that surrounds the nuclei of neurons and neuroglia.

Ganglia Structure and Function

Ganglia are ovoid structures containing neuronal cell bodies and glial cells supported by connective tissue, acting as relay stations for nerve impulses. Sensory ganglia contain the cell bodies of sensory neurons, which are unipolar and enveloped by cuboidal capsule cells. These include cranial and spinal ganglia. Autonomic ganglia contain the cell bodies of postganglionic autonomic nerves, which are multipolar neurons enveloped by satellite cells. Some are intramural, meaning they are located within the walls of specific organs.

Clinical Applications in Neurology

Several clinical conditions arise from damage to specific nervous system components. Cerebellar ataxia results from damage to the cerebellar cortex, leading to poor coordination of voluntary movement and loss of balance. Causes include tumors, trauma, alcohol, and hypoxia.

Poliomyelitis involves the destruction of alpha motor neurons, causing permanent flaccid paralysis, also known as lower motor neuron (LMN) paralysis, where muscles lose tone. Parkinson's disease is a neurodegenerative disorder characterized by tremor, muscular rigidity, and bradykinesia. It is caused by the death of neurons in the substantia nigra, leading to a significant reduction in dopamine levels in the brain.