# Lecture 9: Nervous Tissue - Neurons ## Unit 1.2: Histology and Basic Tissues --- ## Learning Objectives By the end of this lecture, students will be able to: 1. Describe the structural components of neurons including cell body, dendrites, and axon 2. Classify neurons by number of processes (unipolar, bipolar, multipolar) and by function (sensory, motor, interneuron) 3. Explain the ultrastructural features of neurons including Nissl bodies, neurofilaments, and synaptic structures 4. Describe the structure and function of synapses and the process of synaptic transmission 5. Identify different types of neurons in histological sections 6. Explain the concepts of anterograde and retrograde axonal transport --- ## Introduction to Nervous Tissue Nervous tissue represents the most specialized tissue in the body for receiving, integrating, and transmitting information. This tissue is responsible for all conscious and unconscious activity, from simple reflexes to complex thought processes, memory formation, and emotional responses. Nervous tissue comprises two fundamental cell types that work in concert: neurons and glial cells (neuroglia). Neurons are the excitable cells that generate and conduct electrical signals, processing information through elaborate networks of connections. Glial cells provide essential support functions including structural scaffolding, metabolic support, myelination, and immune defense. Both cell types arise from neuroectoderm during embryonic development, with the notable exception of microglia, which derive from mesoderm. The nervous system is anatomically divided into two major components. The central nervous system encompasses the brain and spinal cord, where neurons are organized into complex processing centers. The peripheral nervous system includes all nervous tissue outside the CNS, consisting primarily of nerves that carry signals between the CNS and the rest of the body, along with ganglia that contain neuronal cell bodies. Panel A: Human body silhouette with brain and spinal cord highlighted in blue as CNS and peripheral nerves radiating throughout body in green as PNS showing anatomical organization. Panel B: Detailed multipolar neuron inset with purple soma containing Nissl bodies, multiple branching orange dendrites, and single blue axon with myelin segments. Panel C: Glial cell relationship inset showing star-shaped astrocytes, oligodendrocytes wrapping axons, and small microglial cells scattered throughout neural tissue. Panel D: Magnified neural tissue histology view showing labeled neurons and surrounding neuropil with leader lines identifying all structures. --- ## Neuron Structure ### The Cell Body (Soma) The cell body, also called the soma or perikaryon, serves as the biosynthetic and metabolic center of the neuron. Neuronal cell bodies vary considerably in size, ranging from just 5 micrometers in small interneurons to an impressive 135 micrometers in large motor neurons. Despite this size variation, all neurons share fundamental structural features that reflect their high metabolic demands. The nucleus dominates the cell body and presents several distinctive characteristics. It is typically large, spherical, and centrally positioned, with pale-staining chromatin that appears euchromatic due to the high transcriptional activity required to maintain the extensive neuronal processes. A prominent nucleolus is often visible, reflecting the intense ribosomal RNA synthesis needed for protein production. The cytoplasm of the cell body contains several characteristic organelles. Most distinctive are the Nissl bodies, which appear as basophilic clumps throughout the cytoplasm. These represent aggregates of rough endoplasmic reticulum studded with ribosomes and clusters of free polyribosomes, all dedicated to the massive protein synthesis requirements of neurons. The Golgi apparatus is well-developed, often surrounding the nucleus, processing proteins for transport throughout the cell. Mitochondria are abundant, supplying the ATP needed for maintaining ionic gradients, synthesizing neurotransmitters, and powering cellular machinery. The neuronal cytoskeleton is particularly prominent and includes neurofilaments, which are intermediate filaments providing structural support, along with microtubules that serve as tracks for intracellular transport. With aging, neurons accumulate lipofuscin, a golden-brown pigment composed of lysosomal residual bodies that represents accumulated oxidative damage over the life of the cell. ### Dendrites Dendrites are the receptive processes of neurons, designed to receive incoming signals from other neurons. Most neurons possess multiple dendrites that extend from the cell body and branch extensively, creating an elaborate dendritic tree that vastly expands the receptive surface area of the neuron. Unlike axons, dendrites contain Nissl bodies, at least in their proximal portions near the cell body. This allows for local protein synthesis to support synaptic function. As dendrites branch, they progressively taper, becoming thinner with each division. The surfaces of many dendrites are studded with dendritic spines, small mushroom-shaped or stubby protrusions that serve as the primary sites of excitatory synaptic contact. The morphology and number of dendritic spines can change with experience and learning, representing a structural basis for synaptic plasticity. ### The Axon Each neuron possesses a single axon, the process responsible for conducting signals away from the cell body to distant targets. The axon originates from a specialized region of the soma called the axon hillock, a pale-staining conical region that lacks Nissl bodies and marks the transition from cell body to axon. Just beyond the axon hillock lies the initial segment, which contains the highest density of voltage-gated sodium channels and serves as the trigger zone where action potentials are initiated. Unlike dendrites, axons maintain a uniform diameter throughout their length, which can extend from a few millimeters to over a meter in the case of motor neurons innervating distal muscles. Axons may give off collateral branches along their course, allowing a single neuron to influence multiple targets. The axon terminates in synaptic endings called terminal boutons or synaptic terminals, which contain the machinery for neurotransmitter release. The axoplasm differs from the cytoplasm of the cell body in several important ways. Nissl bodies are completely absent, meaning no protein synthesis occurs within the axon. Instead, all proteins and organelles must be transported from the soma. The axon contains abundant neurofilaments and microtubules that serve as the cytoskeletal framework and transport tracks. At synaptic terminals, mitochondria accumulate in large numbers to supply ATP for the energy-intensive processes of neurotransmitter synthesis, packaging, release, and recycling. Panel A: Complete multipolar neuron center with purple cell body soma containing large pale nucleus with dark nucleolus, blue-stained Nissl bodies in cytoplasm, and yellow-gold Golgi apparatus around nucleus. Panel B: Multiple orange dendrites extending from soma with progressively thinner branches and small mushroom-shaped dendritic spines visible at high magnification on dendrite surface. Panel C: Single blue axon emerging from pale axon hillock region devoid of Nissl staining with arrow indicating initial segment and periodic light blue myelin segments with labeled nodes of Ranvier gaps. Panel D: Terminal bouton cluster detail inset showing small synaptic vesicle circles and mitochondria with 50 micrometer main scale and 2 micrometer inset scale with leader line labels. --- ## Neuron Classification ### Classification by Number of Processes Neurons are classified morphologically according to the number and arrangement of their processes emerging from the cell body. This classification reflects both developmental origin and functional specialization. Multipolar neurons represent the most common neuronal type in the nervous system. As the name suggests, these neurons have multiple processes extending from the cell body, typically consisting of numerous dendrites and a single axon. The dendrites may branch extensively, creating elaborate dendritic trees. Examples of multipolar neurons include motor neurons of the spinal cord with their large cell bodies and extensive dendritic arborizations, pyramidal cells of the cerebral cortex with their characteristic triangular cell bodies and prominent apical dendrites, and Purkinje cells of the cerebellar cortex with their spectacular planar dendritic trees. Bipolar neurons have an elongated cell body with a single process emerging from each pole, one serving as the dendrite and the other as the axon. This morphology is well-suited for sensory functions where signals need to be conveyed from a receptor structure to the CNS. Bipolar neurons are found in specialized sensory locations including the retina where they relay signals from photoreceptors, the olfactory epithelium where they detect odor molecules, and the vestibular and spiral ganglia where they transmit balance and auditory information. Unipolar neurons, more accurately termed pseudounipolar neurons, have a single process that emerges from the cell body and then bifurcates into two branches. The cell body appears to be located off to the side of the main conduction pathway. This configuration is characteristic of primary sensory neurons in dorsal root ganglia and cranial nerve sensory ganglia. In these neurons, one branch extends to the periphery to detect sensory stimuli while the other projects centrally to the spinal cord or brainstem. Action potentials can propagate past the cell body without having to traverse it, allowing for rapid signal transmission. Panel A: Multipolar neuron with star-shaped appearance showing large central purple cell body, multiple branching orange dendrites extending in all directions, and single blue axon from axon hillock extending downward with examples of motor neuron, pyramidal cell, and Purkinje cell. Panel B: Bipolar neuron with elongated oval purple cell body, single orange dendrite extending upward and single blue axon extending downward creating symmetrical appearance with examples of retinal bipolar cells and olfactory neurons. Panel C: Pseudounipolar neuron with round purple cell body positioned to side with single process bifurcating into T-shape with orange peripheral branch toward sensory receptor and blue central branch toward spinal cord with dorsal root ganglion neuron example. Panel D: All neuron types drawn to same 50 micrometer scale with light gray background outlines indicating typical nervous system locations for each morphological type. ### Classification by Function Neurons are also classified according to their role in neural circuits. Sensory neurons, also called afferent neurons, carry information from sensory receptors toward the central nervous system. These neurons detect stimuli ranging from light and sound to temperature, pain, touch, and chemical signals. Their cell bodies are typically located in ganglia outside the CNS. Motor neurons, or efferent neurons, carry information away from the central nervous system to control effector organs. Somatic motor neurons innervate skeletal muscle and are under voluntary control, while autonomic motor neurons innervate smooth muscle, cardiac muscle, and glands as part of the autonomic nervous system. Interneurons, also known as association neurons, represent the vast majority of neurons in the nervous system. These neurons are entirely contained within the central nervous system and serve to connect sensory and motor pathways, performing the integration and processing that underlies complex behavior. Interneurons may be excitatory or inhibitory and form the intricate circuits responsible for all higher brain functions. --- ## Neuronal Ultrastructure ### Nissl Bodies Nissl bodies, also called Nissl substance or tigroid substance, are the most distinctive ultrastructural feature of neurons. Under electron microscopy, they reveal themselves as parallel stacks of rough endoplasmic reticulum studded with ribosomes, along with clusters of free polyribosomes between the ER cisternae. This organization reflects the enormous protein synthesis capacity of neurons, which must produce proteins for the cell body plus all the extending processes. Nissl bodies stain intensely basophilic with basic dyes due to the high concentration of ribosomal RNA. They are found throughout the cell body and extend into the proximal portions of dendrites but are notably absent from the axon hillock and the entire axon. This distribution makes the axon hillock identifiable as a pale region at the origin of the axon. When a neuron is injured, particularly through axon damage, a characteristic response called chromatolysis occurs. The Nissl bodies disperse and seem to dissolve, the nucleus moves from its central position to the cell periphery, and the cell body swells. This response represents a shift in protein synthesis from maintenance mode to regeneration mode, as the cell attempts to produce proteins needed for axon regrowth. Depending on the severity and location of injury, chromatolysis may be followed by successful regeneration or by neuronal death. ### Cytoskeletal Elements The neuronal cytoskeleton is crucial for maintaining cell shape, supporting the extended processes, and enabling intracellular transport. Three major filament types comprise the cytoskeleton: neurofilaments, microtubules, and microfilaments. Neurofilaments are the intermediate filaments of neurons, measuring approximately 10 nanometers in diameter. They are composed of three subunit proteins (NF-L, NF-M, and NF-H) that assemble into stable rope-like structures providing tensile strength and maintaining the caliber of axons. Neurofilaments are synthesized in the cell body and slowly transported down the axon. Abnormal accumulation of neurofilaments is observed in several neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and Parkinson's disease, where phosphorylated neurofilaments aggregate inappropriately. Microtubules are hollow tubes approximately 25 nanometers in diameter, assembled from tubulin subunits. They serve as the tracks for motor protein-dependent transport of organelles and vesicles. In axons, microtubules are uniformly oriented with their plus ends (the growing ends) directed toward the axon terminal. In dendrites, microtubules have mixed polarity. This orientation difference has functional implications for the directionality of transport. Microfilaments composed of actin are particularly important in specialized structures including growth cones at the tips of developing or regenerating axons, and dendritic spines where actin dynamics underlie synaptic plasticity. Panel A: High magnification Nissl body showing parallel blue-purple rough endoplasmic reticulum cisternae arrays studded with small dark ribosome dots and free polyribosomes in between at 500 nanometer scale. Panel B: Golgi apparatus showing yellow-gold stacked cisternae with budding vesicles demonstrating protein processing and transport preparation. Panel C: Longitudinal axon section showing parallel thin gray neurofilaments and microtubules as hollow circles in cross-section and parallel tracks longitudinally with visible motor protein projections. Panel D: Mitochondria as elongated organelles with cristae clustered at synaptic terminal plus center diagram showing relationship of all structures within neuron cell body with labeled leader lines on gray EM background. ### Axonal Transport Because the axon lacks ribosomes and cannot synthesize proteins, all proteins, organelles, and other materials needed in the axon and synaptic terminal must be transported from the cell body. This axonal transport is absolutely essential for neuronal function and survival. Anterograde transport moves materials from the cell body toward the axon terminal. This is accomplished by kinesin motor proteins that walk along microtubules toward the plus ends. Fast anterograde transport moves at 100 to 400 millimeters per day and carries membrane-bound organelles including synaptic vesicles and their precursors, mitochondria, and membrane proteins. Slow anterograde transport moves at 1 to 10 millimeters per day and conveys cytoskeletal proteins and cytoplasmic enzymes that maintain axonal structure and metabolism. Retrograde transport moves materials from the axon terminal back toward the cell body. This is powered by dynein motor proteins walking toward the microtubule minus ends. Retrograde transport operates at speeds of 200 to 300 millimeters per day and carries endocytic vesicles containing recycled membrane, degraded materials destined for lysosomal processing, and importantly, signaling molecules such as neurotrophic factors that inform the cell body about conditions at the synapse. Retrograde transport is exploited by certain pathogens as a route to reach neuronal cell bodies. Rabies virus and herpes simplex virus enter neurons at peripheral sites and travel via retrograde transport to the cell body, where they replicate. This mechanism explains how rabies virus can travel from a bite wound to the brain. Panel A: Longitudinal axon section with parallel green microtubule tracks showing anterograde transport with blue Y-shaped kinesin motor protein walking toward plus end carrying purple vesicle circles and brown mitochondrion at fast 100-400 mm per day or slow 1-10 mm per day speeds. Panel B: Retrograde transport with red dynein motor protein walking toward minus end carrying dark endosome and NGF-labeled signaling endosome at 200-300 mm per day speed. Panel C: Cell body inset with nucleus as origin of anterograde materials and terminal bouton inset with synaptic vesicles as destination with arrows indicating direction of movement throughout. Panel D: Small icons indicating rabies virus and herpes virus exploiting retrograde transport pathway to reach neuronal cell bodies from peripheral sites. --- ## The Synapse ### Overview The synapse is the specialized junction where neurons communicate with other neurons or with effector cells such as muscle fibers or gland cells. The human brain contains an estimated 100 trillion synapses, forming the complex networks that underlie all neural function. The term "synapse" comes from the Greek word for "clasp" or "join," reflecting the close relationship between the communicating cells. Two fundamentally different types of synapses exist. Chemical synapses are by far the most common and involve release of neurotransmitter molecules from the presynaptic cell, diffusion across a synaptic cleft, and binding to receptors on the postsynaptic cell. This mechanism allows for unidirectional signal flow and introduces a slight synaptic delay, but provides the opportunity for signal modulation and plasticity. Electrical synapses, formed by gap junctions between neurons, allow direct passage of ions between cells. Electrical synapses are faster, bidirectional, and synchronize activity between connected neurons, but lack the modulatory capacity of chemical synapses. ### Structure of Chemical Synapses The chemical synapse consists of three components that work together to enable signal transmission: the presynaptic terminal, the synaptic cleft, and the postsynaptic membrane. The presynaptic terminal, also called the synaptic bouton, is a specialized ending of the axon that contains the machinery for neurotransmitter release. The most prominent feature is the collection of synaptic vesicles, small membrane-bound spheres approximately 40 to 50 nanometers in diameter containing neurotransmitter molecules. These vesicles cluster near a specialized region of the presynaptic membrane called the active zone, where vesicle fusion and neurotransmitter release occur. The active zone contains voltage-gated calcium channels and the protein machinery needed for vesicle docking and fusion. Mitochondria are abundant in synaptic terminals, providing ATP for vesicle recycling, neurotransmitter synthesis, and maintenance of ion gradients. The synaptic cleft is the narrow extracellular space, typically 20 to 30 nanometers wide, that separates the presynaptic and postsynaptic membranes. This cleft contains extracellular matrix material and adhesion molecules that hold the pre- and postsynaptic elements in close registration. Neurotransmitter molecules diffuse across this gap to reach postsynaptic receptors. The postsynaptic membrane contains the receptors that respond to released neurotransmitter. Immediately beneath the membrane is the postsynaptic density, an electron-dense collection of scaffolding proteins, signaling molecules, and cytoskeletal elements that anchors receptors and organizes the signaling machinery. The postsynaptic density is particularly prominent at excitatory synapses. Panel A: Blue-gray presynaptic terminal as swollen bouton containing numerous small purple synaptic vesicles at 40-50 nm clustered at active zone near membrane with brown mitochondria with cristae in background and microtubules entering from axon. Panel B: Active zone marked with vesicles docked at membrane and red voltage-gated calcium channel transmembrane proteins adjacent plus cream-tan synaptic cleft as 20-30 nm space with wispy extracellular matrix bridging gap. Panel C: Orange postsynaptic membrane with dark gray postsynaptic density band beneath membrane containing green receptor proteins and visible dendritic spine structure below. Panel D: Magnified inset of vesicle fusion with SNARE proteins at 200 nanometer scale with all structures labeled with leader lines throughout. --- ## Synaptic Transmission ### The Steps of Chemical Transmission Synaptic transmission at a chemical synapse follows a precise sequence of events that converts an electrical signal in the presynaptic neuron into a chemical signal that crosses the cleft and then back into an electrical or biochemical response in the postsynaptic cell. The process begins when an action potential propagating along the axon reaches the presynaptic terminal. The depolarization of the terminal membrane activates voltage-gated calcium channels concentrated at the active zone. Calcium ions rush into the terminal down their electrochemical gradient, and this calcium influx is the essential trigger for neurotransmitter release. The elevated calcium concentration triggers fusion of synaptic vesicles with the presynaptic membrane, a process mediated by SNARE proteins (soluble NSF attachment protein receptors). The vesicle membrane fuses with the plasma membrane, releasing neurotransmitter molecules into the synaptic cleft through exocytosis. A single action potential typically triggers fusion of hundreds of vesicles at a synapse. Released neurotransmitter molecules diffuse rapidly across the narrow synaptic cleft and bind to specific receptors on the postsynaptic membrane. Depending on the receptor type, this binding either directly opens ion channels (ionotropic receptors) or activates intracellular signaling cascades through G-proteins (metabotropic receptors). The postsynaptic response depends on the neurotransmitter and receptor involved. Excitatory postsynaptic potentials (EPSPs) are depolarizations that bring the postsynaptic cell closer to firing threshold, typically produced by glutamate acting on its receptors. Inhibitory postsynaptic potentials (IPSPs) are hyperpolarizations or stabilizations of membrane potential that reduce the likelihood of firing, typically produced by GABA or glycine. Finally, neurotransmitter action must be terminated to prepare for the next signal. This occurs through enzymatic degradation within the cleft (as with acetylcholinesterase breaking down acetylcholine), reuptake into the presynaptic terminal via specific transporter proteins (as with dopamine, serotonin, and norepinephrine), or simple diffusion away from the synapse. The presynaptic terminal then recycles vesicle membrane and refills vesicles with neurotransmitter for subsequent rounds of release. ### Neurotransmitters Neurotransmitters are chemically diverse molecules unified by their function as synaptic signaling molecules. Amino acid transmitters include glutamate, the main excitatory transmitter in the brain, and GABA (gamma-aminobutyric acid) and glycine, the principal inhibitory transmitters. Monoamines include dopamine, involved in reward, movement, and cognition; norepinephrine, important for arousal and stress responses; serotonin, involved in mood regulation; and histamine, contributing to arousal and allergic responses. Acetylcholine functions at the neuromuscular junction and in various brain circuits. Neuropeptides such as substance P, endorphins, and neuropeptide Y act as neuromodulators. Other signaling molecules include ATP and the gas nitric oxide. ### Receptor Types Postsynaptic receptors fall into two major categories with distinct mechanisms and timescales. Ionotropic receptors, also called ligand-gated ion channels, are receptor proteins that contain an integral ion channel. Neurotransmitter binding directly opens the channel, producing rapid responses within milliseconds. Examples include AMPA and NMDA glutamate receptors, GABA-A receptors, and nicotinic acetylcholine receptors. Metabotropic receptors are G-protein-coupled receptors that activate intracellular signaling cascades when bound by neurotransmitter. These produce slower but more sustained effects, often modulating neuronal excitability over seconds to minutes. Examples include dopamine receptors, muscarinic acetylcholine receptors, and metabotropic glutamate receptors. Panel A: Steps 1-2 showing lightning bolt action potential arriving at blue presynaptic bouton with vesicles then red voltage-gated calcium channel rectangles opening with green calcium ions flowing inward. Panel B: Steps 3-4 showing calcium binding sensor proteins triggering vesicle movement with SNARE complex twisted proteins then omega-shaped fusion pore releasing red triangle neurotransmitter molecules into cleft. Panel C: Steps 5-7 showing neurotransmitter diffusing across 20-30 nm cleft then binding green Y-shaped postsynaptic receptors on orange membrane then ionotropic channel opening or metabotropic G-protein activation with ions entering or second messenger cascade. Panel D: Step 8 showing neurotransmitter removal by blue reuptake transporter pump, scissors enzyme degradation icon, or diffusion arrows plus center oscilloscope-style EPSP and IPSP waveforms with all steps numbered and arrow-connected. --- ## Types of Synapses by Location Synapses are also classified according to where on the postsynaptic neuron the presynaptic terminal makes contact. Axodendritic synapses, where an axon terminal contacts a dendrite or dendritic spine, are the most common type. These synapses are typically excitatory and occur on dendritic spines, placing them at some distance from the cell body. Axosomatic synapses form where axon terminals contact the cell body directly. Because they are close to the axon hillock, these synapses exert powerful influence over whether the postsynaptic neuron will fire. Many axosomatic synapses are inhibitory, strategically positioned to suppress neuronal output. Axoaxonic synapses occur where one axon terminal contacts another axon, typically near its terminal. These synapses modulate neurotransmitter release from the contacted axon, either facilitating or inhibiting transmission at that synapse. This provides a mechanism for presynaptic modulation of synaptic strength. Dendrodendritic synapses, where dendrites make synaptic contact with each other, occur in specialized regions such as the olfactory bulb and retina. These allow for local processing within dendrites without involving action potential propagation. --- ## Neuronal Cell Types in the CNS Different regions of the central nervous system contain characteristic neuron types adapted to their specific functions. Pyramidal cells are the principal excitatory neurons of the cerebral cortex and hippocampus. They are named for their triangular-shaped cell bodies. A prominent apical dendrite extends toward the cortical surface, while basal dendrites spread laterally. Pyramidal cells use glutamate as their neurotransmitter and form the major projection neurons of the cortex, with axons that may travel to distant cortical or subcortical targets. Purkinje cells are among the most distinctive neurons in the nervous system, located in the cerebellar cortex. They possess extraordinarily elaborate dendritic trees that spread in a single plane, like a fan or espalier tree. This planar arrangement maximizes synaptic contact with parallel fibers crossing perpendicularly through the dendritic field. Despite their enormous dendritic trees, Purkinje cells are inhibitory, releasing GABA onto their target neurons in the cerebellar nuclei. Granule cells are small neurons found in high density in the cerebellar cortex and hippocampal dentate gyrus. In the cerebellum, granule cells are the most numerous neurons in the brain, with an estimated 50 billion in humans. Their axons ascend and bifurcate to form parallel fibers. Motor neurons in the anterior horn of the spinal cord are large multipolar neurons with extensive dendritic trees that receive convergent input from descending pathways and spinal circuits. Their axons exit the spinal cord and travel to skeletal muscles, often over considerable distances. Panel A: Pyramidal cell from cerebral cortex with triangular purple cell body, prominent orange apical dendrite extending upward with branches, horizontal orange basal dendrites, and single descending blue axon with faint cortical layer background. Panel B: Purkinje cell from cerebellar cortex with large round purple cell body and spectacular planar orange dendritic tree extending upward like elaborate fan with thin gray parallel fibers crossing perpendicular and single downward blue axon. Panel C: Granule cells as cluster of small round densely packed purple cell bodies with thin ascending axons bifurcating into T-shaped parallel fibers showing smallest relative size. Panel D: Spinal motor neuron with large multipolar purple cell body, extensive radiating orange dendrites filling space, and thick blue axon projecting toward muscle icon with each panel labeled for neuron type, location, and neurotransmitter. --- ## Histological Staining for Neurons Different staining techniques reveal different aspects of neuronal structure and are selected based on what the investigator wishes to demonstrate. Routine hematoxylin and eosin staining provides general morphology. Nissl bodies appear basophilic (blue-purple) due to their RNA content, while the neuropil appears eosinophilic (pink). Neuronal nuclei are pale with prominent nucleoli. Nissl staining with cresyl violet or thionin specifically highlights Nissl substance, staining neurons a deep purple. This technique is excellent for demonstrating neuronal cell bodies and their distribution, allowing for cytoarchitectural mapping of the brain. Golgi silver impregnation staining randomly labels a small percentage of neurons but reveals their complete morphology including all dendrites and the axon in striking detail. Neurons appear as black silhouettes against a golden-brown background. This technique, developed in the 1870s, revealed the true complexity of neuronal form. Myelin stains such as Luxol Fast Blue highlight myelinated axons, staining white matter blue while leaving gray matter pale. This is useful for demonstrating myelinated fiber tracts. Immunohistochemistry uses antibodies to localize specific proteins, allowing identification of neuronal subtypes based on their neurotransmitters, receptors, or other molecular markers. --- ## Clinical Correlations ### Chromatolysis When a neuron's axon is damaged, the cell body undergoes a characteristic response called chromatolysis. Within days of axon injury, the Nissl bodies appear to dissolve and disperse, the nucleus moves from its central position to the periphery of the cell, and the cell body swells. These changes reflect a fundamental shift in the cell's synthetic priorities from maintaining steady-state function to attempting regeneration. The outcome depends on many factors: peripheral nerve axons can regenerate successfully if the injury allows, while central nervous system axons generally cannot regenerate, and severe injuries may lead to neuronal death. ### Neurodegenerative Diseases Several devastating neurological diseases involve abnormal protein accumulation in neurons. In Alzheimer's disease, neurofibrillary tangles composed of hyperphosphorylated tau protein accumulate within neurons, disrupting cytoskeletal function and eventually causing cell death. Parkinson's disease involves the progressive loss of dopaminergic neurons in the substantia nigra, with surviving neurons containing Lewy bodies composed primarily of aggregated alpha-synuclein protein. Amyotrophic lateral sclerosis (ALS) involves the death of motor neurons, often associated with abnormal accumulation of neurofilaments and other proteins. ### Viral Exploitation of Axonal Transport Certain neurotropic viruses exploit retrograde axonal transport to reach neuronal cell bodies. Rabies virus enters neurons at peripheral sites, such as a bite wound, and travels via retrograde transport to reach the central nervous system. Herpes simplex virus similarly uses retrograde transport to reach sensory ganglia where it establishes latent infection. In rabies, characteristic eosinophilic cytoplasmic inclusions called Negri bodies form in infected neurons and are diagnostic of the infection. --- ## Summary Neurons are the functional units of the nervous system, specialized for receiving, processing, and transmitting information. They consist of a cell body containing the nucleus and biosynthetic machinery, dendrites that receive incoming signals, and a single axon that conducts signals to targets. Nissl bodies, the aggregates of rough endoplasmic reticulum responsible for protein synthesis, are found in the cell body and dendrites but are absent from the axon hillock and axon. Neurons are classified by their morphology as multipolar (most common, with many dendrites), bipolar (one dendrite and one axon), or pseudounipolar (single bifurcating process). They are functionally classified as sensory neurons carrying information toward the CNS, motor neurons carrying commands to effectors, or interneurons connecting and processing within the CNS. Axonal transport moves materials between cell body and terminals: anterograde transport via kinesin carries vesicles and organelles toward the terminal, while retrograde transport via dynein returns materials to the soma. Chemical synapses transmit signals through neurotransmitter release, diffusion across the synaptic cleft, and receptor activation on the postsynaptic cell. Different CNS regions contain characteristic neuron types adapted to specific functions. --- ## Key Terms | Term | Definition | |------|------------| | Nissl bodies | Aggregates of rough endoplasmic reticulum and ribosomes in neurons responsible for protein synthesis | | Axon hillock | The pale-staining region where the axon originates from the cell body, lacking Nissl bodies | | Synapse | Specialized junction for communication between neurons or between neurons and effector cells | | Neurotransmitter | Chemical messenger released at synapses to transmit signals to postsynaptic cells | | Anterograde transport | Movement of materials from the cell body toward the axon terminal via kinesin motors | | Retrograde transport | Movement of materials from the axon terminal toward the cell body via dynein motors | --- *This content is subject to the [MIT License](https://opensource.org/licenses/MIT). © 2024–2026 Hibbert School of Medicine.*