Neuron and Neuroglia Detailed Study Guide

General Overview of Neurons

  • Definition: A neuron is the name given to the nerve cell and all of its processes.
  • Functional Specialization: Neurons are excitable cells specialized for the reception of stimuli and the conduction of the nerve impulse.
  • Anatomical Location: Neurons are found within the central nervous system (brain and spinal cord) as well as in peripheral ganglia.
  • Replicative Ability: Unlike most other somatic cells in the human body, mature neurons do not undergo cell division and replication.

Morphologic and Functional Classification of Neurons

Classification Based on Neurite Arrangement

Neurons are classified according to the number, length, and mode of branching of their neurites (processes):

  • Unipolar Neurons:
    • Morphology: A single neurite emerges from the cell body and divides a short distance away into two branches.
    • Location: Found in the posterior root ganglion.
  • Bipolar Neurons:
    • Morphology: A single neurite emerges from either end of an elongated cell body.
    • Location: Found in the retina, sensory cochlear ganglia, and vestibular ganglia.
  • Multipolar Neurons:
    • Morphology: Possess many dendrites and one long axon.
    • Location: Found in the fiber tracts of the brain and spinal cord, peripheral nerves, and motor cells of the spinal cord.
  • Pseudo-unipolar Neurons:
    • Morphology: Possesses processes that appear as a single axon with no true dendrites; the axon branches function structurally and functionally as a single continuous axon.

Classification Based on Neuron Size

  • Golgi Type I Neurons:
    • Morphology: Characterized by a single long axon.
    • Location: Fiber tracts of the brain and spinal cord, peripheral nerves, motor cells of the spinal cord, pyramidal cells of the cerebral cortex, and Purkinje cells of the cerebellar cortex.
  • Golgi Type II Neurons:
    • Morphology: Characterized by a short axon that, together with its dendrites, gives the cell a star-like appearance.
    • Location: Cerebral cortex and cerebellar cortex.

Specific Neuronal Types Across Neural Regions

  • Cerebellar Cortex: Stellate cells, granule cells, and Purkinje cells.
  • Cerebral Cortex: Pyramidal cells (upper motor neurons) and Golgi type II interneurons.
  • Spinal Cord: Lower motor neurons in the anterior horn.

Detailed Structures of a Neuron

Cell Body (Perikaryon)

  • Structure: Consists of a mass of cytoplasm in which a nucleus is embedded, bounded externally by a plasma membrane.
  • Volume Distribution: The volume of cytoplasm contained within the cell body is often far less than the combined total volume of cytoplasm in its neurites.

Nucleus

  • Function: Stores the genetic material (chromosomes, chromatin, DNA).
  • Location: Typically centrally located within the cell body, appearing large and rounded.
  • Displacement: Under conditions of neuronal injury or fatigue, the nucleus is displaced to the periphery of the cell body.
  • Nucleolus: Usually contains a single prominent nucleolus concerned directly with ribosomal synthesis and protein production.
  • Barr Body: In females, one of the two XX chromosomes is compact and visible as the Barr body.

Nuclear Envelope

  • Structure: Can be regarded as a specialized portion of the rough endoplasmic reticulum (rough ER). It consists of a double-layered membrane separated by a perinuclear space.
  • Pores: Possesses fine nuclear pores through which materials diffuse into and out of the nucleoplasm.
  • Associated Structures: The outer membrane is studded with ribosomes and continuous with the rough ER.

Cytoplasm and Organelles

The cytoplasm is rich in granular (rough) and agranular (smooth) endoplasmic reticulum and contains the following specialized organelles and inclusions:

  • Nissl Substance:

    • Structure: Consists of prominent basophilic granules distributed throughout the cytoplasm of the cell body and proximal regions of dendrites.
    • Exclusions: Completely absent in the axon hillock (the region of the cell body adjacent to the axon) and within the axon itself.
    • Function: Responsible for protein synthesis.
    • Chromatolysis: Neuronal fatigue or mechanical damage causes the Nissl substance to redistribute and concentrate at the periphery of the cytoplasm. This gives the optical impression that the Nissl substance has dissolved or disappeared.

  • Golgi Complex:

    • Structure: Network of irregular, wavy threads surrounding the nucleus composed of flattened cisternae and small vesicles of smooth ER.
    • Function: Receives proteins produced by the Nissl substance via transport vesicles. Temporarily stores these proteins and adds carbohydrate moieties to form glycoproteins. Active in lysosome formation and cell membrane synthesis.

  • Mitochondria:

    • Structure: Spherical or rod-shaped organelles scattered throughout the cell body, dendrites, and axon. The wall exhibits a double membrane, with the inner membrane folded into cristae projecting into the central matrix.
    • Function: Possesses respiratory and metabolic enzymes that generate adenosine triphosphate (ATPATP) for cellular energy.

  • Microfilaments:

    • Structure: Measure approximately 3−5 nm3-5\,nm in diameter and are composed of actin.
    • Location: Concentrated at the periphery of the cytoplasm immediately beneath the plasma membrane.
    • Function: Work with microtubules to form new cell processes, retract old ones, and assist in axonal transport.

  • Neurofilaments (Intermediate Filaments):

    • Structure: Measure approximately 10 nm10\,nm in diameter and aggregate into larger bundles called neurofibrils.
    • Function: Form the primary structural component of the neuronal cytoskeleton.

  • Microtubules:

    • Structure: Measure approximately 25 nm25\,nm in diameter and are interspersed among neurofilaments.
    • Function: Provide structural rigidity and serve as tracks for intracellular transport.

  • Lysosomes:

    • Structure: Membrane-bound vesicles measuring approximately 8 nm8\,nm in diameter containing hydrolytic enzymes.
    • Origin: Formed by budding from the Golgi complex.
    • Functional States:
    1. Primary Lysosomes: Newly formed vesicles.
    2. Secondary Lysosomes: Contain partially digested cellular debris.
    3. Residual Bodies: Vesicles in which enzymatic digestion is complete and enzymes are inactive.

  • Centrioles:

    • Structure: Small, paired hollow cylindrical structures whose walls consist of bundles of microtubules.
    • Function: Present in immature dividing nerve cells; retained in mature, non-dividing neurons where they participate in maintaining microtubule integrity.

  • Cytoplasmic Inclusions and Pigments:

    • Lipofuscin: Yellowish-brown pigment granules formed as a harmless metabolic by-product of lysosomal activity; accumulates in the cytoplasm with advancing age.
    • Melanin: Pigment granules found in the cytoplasm of neurons in specific brain regions, such as the substantia nigra of the midbrain. Presence is associated with the synthesis of catecholamine neurotransmitters, specifically dopamine.
    • Glycogen and Lipids: Stored nutrients present in cytoplasm.

Intracellular Axonal Transport

Intracellular transport involves the movements of membrane organelles, secretory material, synaptic precursor membranes, large dense-core vesicles, mitochondria, and smooth ER across the cell body and processes in both directions.

  • Rapid Axonal Transport:
    • Rate: Moves materials at a speed of 100−400 mm100-400\,mm per day.
    • Motor Proteins:
    • Kinesin: Mediates anterograde transport (movement away from the cell body toward process terminals).
    • Dynein: Mediates retrograde transport (movement from the peripheral processes back toward the cell body).
  • Slow Axonal Transport:
    • Rate: Moves materials at a speed of 0.1−3.0 mm0.1-3.0\,mm per day.
    • Direction: Occurs exclusively in the anterograde direction.
    • Mechanism: Involves bulk flow of cytoplasm including cytoskeletal components, mitochondria, and other organelles. Driven by motor proteins belonging to the kinesin family.

Plasma Membrane and Electrophysiology

Structure of the Plasma Membrane

  • Thickness: Approximately 8 nm8\,nm thick.
  • Composition: Formed by a lipid bilayer consisting of two rows of phospholipid molecules with nonpolar hydrophobic fatty acid tails facing inward and polar hydrophilic phosphate heads facing outward.
  • Proteins and Glycocalyx: Transmembrane protein molecules span the full thickness of the bilayer to form channels and receptors. Carbohydrate chains attach to proteins or lipids on the external surface to form the glycocalyx (cell coat).
  • Permeability: Functions as a semipermeable membrane controlling ionic diffusion.

Resting Potential

  • Magnitude: The unstimulated resting state of a neuron maintains an electrical potential difference equal to −80 mV-80\,mV.
  • Ionic Basis: Potassium (K+K^+) ions diffuse through passive leak channels out of the cell cytoplasm into the tissue fluid. Because membrane permeability to K+K^+ is significantly greater than to sodium (Na+Na^+) ions, a net positive charge accumulates on the outer surface, leaving the inner surface negative relative to the outside.

Action Potential

  • Generation: Initiated when a neuron is stimulated by electrical, mechanical, or chemical means.
  • Depolarization Phase: Na+Na^+ channels open, allowing Na+Na^+ ions to diffuse rapidly into the cytoplasm down their concentration and electrical gradients. The charge inside the cell depolarizes and temporarily reverses polarity to +40 mV+40\,mV.
  • Duration: Extremely brief, lasting approximately 5\,ms$.\n- **Propagation**: Spreads along the length of the plasma membrane away from the site of initiation as a continuous nerve impulse.\n- **Refractory Period**: Following an action potential, the membrane enters a brief nonexcitable state during which another action potential cannot be elicited. This period determines and limits the maximum frequency of impulse conduction.\n\n## Ion Channels and Gating Mechanisms\n\n- **Structure**: Transmembrane proteins spanning the complete width of the plasma membrane form discrete channel pores for Na^+andandK^+.\n- **Conformational States**: Exist in at least two functional states: an *Open* functional state and a *Closed* functional state.\n- **Gating**: Channel opening and closing involves physical twisting and structural distortion of the protein subunits, creating a wider or narrower lumen.\n\n# Structural Characteristics of Neurites\n\n## Dendrites\n\n- **Structure**: Short, highly branched processes extending from the cell body. Finer terminal branches display numerous small projections called dendritic spines.\n- **Cytoplasmic Contents**: Identical to the cell body cytoplasm, containing Nissl granules, mitochondria, microtubules, microfilaments, ribosomes, and agranular ER.\n- **Conduction Direction**: Conducts nerve impulses *toward* the cell body.\n\n## Axons\n\n- **Origin**: Longest single process of the cell body, originating from a specialized conical region termed the axon hillock.\n- **Morphology**: Tubular, uniform in diameter, with a smooth surface. May give off collateral branches along its length (though not near the cell body). Terminates in enlarged endings called axon terminals.\n- **Length Variations**: Ranges from 0.1\,mm(shortlocalinterneuronsintheCNS)to(short local interneurons in the CNS) to3.0\,m (sensory axons extending from peripheral receptors in the toe to the spinal cord and brain).\n- **Conduction Velocity**: Proportional to axonal diameter; larger diameter axons conduct impulses rapidly, while smaller diameter axons conduct slowly.\n- **Axolemma**: The specialized plasma membrane enclosing the axon.\n- **Axoplasm**: The internal cytoplasm of the axon. Lacks both Nissl granules and Golgi complexes.\n- **Initial Segment**: The first 50\text{ to }100\,\mu m of the axon after leaving the axon hillock. Represents the most excitable region of the axon and serves as the physiological site of action potential initiation.\n- **Conduction Direction**: Conducts impulses *away* from the cell body (with the exception of sensory neurons in the posterior root ganglion, where the single long process carries sensory information toward the cell body).\n\n# Synapses\n\n## General Characteristics\n\n- **Definition**: Specialized site where a neuron comes into close physical proximity and functional communication with another neuron, skeletal muscle cell, or gland cell.\n- **Directionality**: Under normal physiological conditions, synaptic transmission proceeds strictly in one direction.\n- **Anatomical Classifications**:\n - *Axodendritic*: Synapse formed between an axon and a dendrite.\n - *Axosomatic*: Synapse formed between an axon and a cell body (soma).\n - *Axoaxonic*: Synapse formed between two axons.\n\n## Chemical Synapses\n\n- **Mechanism**: Communication is mediated by the release of a neurotransmitter across the synaptic cleft, which binds specific receptor proteins on the postsynaptic membrane.\n- **Principal Neurotransmitters**: Primary chemical messengers that act directly on postsynaptic receptors to cause rapid ionic shifts.\n- **Neuromodulators**: Co-released substances that modify, enhance, prolong, or limit the actions of principal neurotransmitters on postsynaptic membranes.\n- **Inactivation Mechanisms**:\n - *Acetylcholine (ACh)*: Effect is terminated by enzymatic degradation within the synaptic cleft via *acetylcholinesterase* (AChE).\n - *Catecholamines*: Effect is terminated primarily by active reuptake back into the presynaptic nerve terminal.\n\n## Electrical Synapses\n\n- **Mechanism**: Direct cytoplasmic connection mediated by gap junction channels spanning presynaptic and postsynaptic membranes.\n- **Prevalence**: Rare within the human central nervous system.\n- **Characteristics**: Does not require chemical neurotransmitters; permits rapid, direct ionic current flow from cell to cell. Conduction is *bidirectional*.\n\n## Classification of Common Neuromediators\n\n| Neuromediator | Functional Role | Target Receptor | Primary Mechanism | Primary Location / Function |\n| :--- | :--- | :--- | :--- | :--- |\n| **Acetylcholine (Nicotinic)** | Principal Neurotransmitter | Ion channel receptor | Opens cation channel (Fast EPSP) | Main sensory and motor systems; rapid excitation |\n| **L-Glutamate** | Principal Neurotransmitter | Ion channel receptor | Opens cation channel (Fast EPSP) | Main sensory and motor systems; rapid excitation |\n| **GABA** | Principal Neurotransmitter | Ion channel receptor | Opens anion channel for Cl^- (Fast IPSP) | Main sensory and motor systems; rapid inhibition |\n| **Acetylcholine (Muscarinic), Serotonin, Histamine, Adenosine** | Neuromodulator | G-protein-coupled receptor | Opens or closes K^+ororCa^{2+} channels (Slow IPSP and Slow EPSP) | Systems controlling homeostasis; modulation and modification of neuronal activity |\n\n*Note: GABA = gamma-aminobutyric acid; EPSP = excitatory postsynaptic potential; IPSP = inhibitory postsynaptic potential.*\n\n# Neuroglia (Glial Cells)\n\n## Overview\n\n- **Definition**: Nonexcitable supporting cells of the nervous system.\n- **Abundance**: Glial cells are smaller than neurons and outnumber them by 5-10 times.\n- **Volume Contribution**: Comprise approximately half the total volume of the brain and spinal cord.\n\n## Structural and Functional Classification of Neuroglia\n\n### 1. Astrocytes\n- **Fibrous Astrocytes**:\n - *Structure*: Small cell bodies, long slender processes, abundant cytoplasmic filaments, perivascular feet.\n - *Location*: White matter.\n- **Protoplasmic Astrocytes**:\n - *Structure*: Small cell bodies, short thick processes with extensive branching, few cytoplasmic filaments, perivascular feet.\n - *Location*: Gray matter.\n- **Functions**: Provide structural framework; function as electrical insulators; limit neurotransmitter diffusion; take up extracellular K^+$$ ions; store glycogen; exhibit phagocytic activity; replace damaged neurons following injury (gliosis); act as conduits for metabolites; synthesize trophic factors.
2. Oligodendrocytes
  • Structure: Small cell bodies with few delicate processes; lack cytoplasmic filaments.
  • Location: Arranged in rows along myelinated nerve fibers and surrounding neuronal cell bodies.
  • Functions: Form myelin sheaths around central nervous system axons; regulate neuronal biochemistry.
3. Microglia
  • Structure: Smallest neuroglial cells with wavy processes bearing fine spines.
  • Location: Scattered throughout the central nervous system.
  • Functions: Inactive in healthy CNS; proliferate during disease, infection, or trauma to execute phagocytosis; supplemented by circulating blood monocytes.
4. Ependyma
  • Ependymocytes:
    • Structure: Cuboidal or columnar cells with apical cilia and microvilli, joined laterally by gap junctions.
    • Location: Line the brain ventricles and the central canal of the spinal cord.
    • Functions: Circulate and absorb cerebrospinal fluid (CSF).
  • Tanycytes:
    • Structure: Possess long basal processes terminating in end-feet upon blood capillaries.
    • Location: Line the floor of the third ventricle.
    • Functions: Transport neuroendocrine substances from CSF to the hypophyseal-portal circulation.
  • Choroidal Epithelial Cells:
    • Structure: Cuboidal cells with folded basal and lateral membranes, joined tightly by apical tight junctions.
    • Location: Cover the surface of the choroid plexuses.
    • Functions: Produce and secrete cerebrospinal fluid (CSF).

Extracellular Space and Blood-Brain Barrier

  • Extracellular Space: Represents a very narrow continuous gap separating adjacent neurons and neuroglial cells. Filled with interstitial tissue fluid, providing a direct pathway for ion and metabolite exchange between blood capillaries and neural tissue.
  • Blood-Brain Barrier: Formed by tight junctions between endothelial cells lining cerebral capillaries, rendering them impermeable to many circulating chemicals and macromolecules to maintain CNS homeostasis.