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Neurons, Nerve fibers, Glia, Myelination

🧠 Explore Neuromuscular Junction Physiology with Dr Faiza 🧠 Understand how a motor nerve communicates with skeletal muscle and converts a nerve impulse into muscle contraction. This lecture explains the structure of the neuromuscular junction, acetylcholine synthesis and release, end plate potential, muscle action potential generation, excitation-contraction coupling, and major clinical disorders such as myasthenia gravis and Lambert-Eaton myasthenic syndrome. It is designed to support concept building, clinical understanding, and preparation for undergraduate, postgraduate, and licensing examinations including USMLE, PLAB, FCPS, NEET PG, and similar exams worldwide. 🎓 Speaker 🎓 Dr Faiza is a physiology educator with qualifications including MBBS as Best Graduate from Allama Iqbal Medical College, FCPS Physiology, MHPE from Riphah International University Islamabad, ICMT, CHPE, DHPE from STMU, MPH from Government College University Faisalabad, and MBA from Virtual University of Pakistan. Her academic expertise includes medical physiology, neurophysiology, muscle physiology, and health professions education. 🎯 Learning Objectives 🎯 Describe the structure of the neuromuscular junction and motor end plate. Explain the organization of the synaptic cleft and junctional folds. Describe the structure and function of nicotinic acetylcholine receptors. Explain the synthesis, storage, release, action, and breakdown of acetylcholine. Describe the ionic basis of the end plate potential. Explain how an end plate potential generates a muscle action potential. Describe the sequence of transmission across the neuromuscular junction. Explain the role of T tubules in excitation-contraction coupling. Discuss the safety factor and fatigue of the neuromuscular junction. Explain the mechanisms of drugs and toxins acting at the neuromuscular junction. Describe the pathophysiology, clinical features, diagnosis, and treatment of myasthenia gravis. Differentiate myasthenia gravis from Lambert-Eaton myasthenic syndrome. 🔬 Topics Covered 🔬 Neuromuscular junction Motor end plate Synaptic gutter and synaptic cleft Subneural and junctional folds Presynaptic nerve terminal Synaptic vesicles and dense bars Nicotinic acetylcholine receptor Fetal and adult acetylcholine receptor subunits Acetylcholine-gated cation channels End plate potential Generation of skeletal muscle action potential Acetylcholine synthesis from choline and acetyl-CoA Choline acetyltransferase Choline transporter Vesicular acetylcholine transporter Acetylcholinesterase Calcium-dependent exocytosis Recycling of synaptic vesicles Clathrin-mediated endocytosis Safety factor at the neuromuscular junction Neuromuscular junction fatigue T tubules Excitation-contraction coupling Hemicholinium Vesamicol Botulinum toxin Curare and d-tubocurarine Anticholinesterase drugs Neostigmine and physostigmine Myasthenia gravis Anti-acetylcholine receptor antibodies Thymic

Health & Medicine◦
Related topics:
Action Potentials•
Physiology of Neuron, Nerve, Glia, Classification & Properties Dr Faiza MBBS (Best Graduate, AIMC Lahore) FCPS Physiology, MHPE (Riphah Int University, Islamabad) ICMT, CHPE, DHPE (STMU) MPH (GC University, Faisalabad) MBA (Virtual University of Pakistan)
2 Learning Objectives • Describe the Physiological anatomy of Neurons • Discuss the axonal transport • Enlist & give functions of Neuroglial cells • Explain process of myelination in Central Nervous System (CNS) & Peripheral Nervous System (PNS) • Classify neurons functionally. • Classify nerve fibers according to Erlanger & Gasser Classification • Enlist properties of nerve fibers.
NEURONS
The Neuron • Soma (Cell Body/Perikaryon) • Metabolic center containing the nucleus and DNA • Neurites • Dendrites • Extensive processes that arborize to receive incoming signals • Axon • Long fibrous process originating from the axon hillock • Initial Segment • The first portion of the axon following the hillock • Presynaptic Terminals • Branching ends of the axon for signal transmission • Synaptic Knobs • Terminal buttons containing vesicles of synaptic transmitters
5 Structure of Neuron Cell Body (Soma) • Enlarged portion of neuron containing cytoplasm and plasma membrane • Contains single, large, centrally located nucleus with prominent nucleolus • Nissl substance: aggregations of rough ER → enzyme synthesis for neurotransmitters • Present in dendrites but absent in axon hillock & axon • Centrosomes (centrioles) observed in mature neurons → maintenance of neurotubules
6 Structure of Neuron Dendrites • Highly branched, short tapering processes • Terminate in sensory receptors or form synapses with neighboring neurons • Some dendrites have dendritic spines (gemmules) • Conduct impulses toward cell body → law of forward conduction / dynamic polarity
7 Structure of Neuron Axon • Arises from axon hillock (cone-shaped portion of soma) • Cylindrical, uniform diameter, variable length • Branches into telodendria → ends in terminal boutons / presynaptic terminals • Plasma membrane = axolemma; • cytoplasm = axoplasm • Initial segment (50–100 μm from axon hillock) → most excitable part → action potential originates
Functional Zones of a Neuron • Input Zone • Dendrites and cell body receive incoming signals • Dendritic Spines Tiny projections that further increase surface area • Protein receptors bind chemical messengers to produce graded potentials • Trigger Zone • The axon hillock (initial segment) initiates action potentials • Axon hillock has the highest density of voltage-gated Na channels • Due to channel density, it is the first region to reach threshold • Conducting Zone • The axon (nerve fiber) transmits action potentials • Axon Length Varies from <1 mm to >1 meter (e.g., spinal cord to big toe) • Output Zone • The highly branched endings known as axon terminals • Terminals release chemical messengers to influence other cells
Morphological Classification of Neurons Based on the number of processes from the soma Bipolar: olfactory epithelium of nasal cavity, sensory ganglia of cochlear and vestibular nerves mesencephalic nucleus of the Vth cranial nerve.
Morphological Classification of Neurons • Unipolar • Single process extending from the cell body • Bipolar • Two distinct processes (one axon, one dendrite) • Pseudounipolar • Single process that divides into two branches • Multipolar • Multiple dendrites and a single axon • Prototypical spinal motor neurons are multipolar in structure
Nerve fibers, Myelination, Axon Transport
Nerve Fiber Anatomy Myelin Sheath: Deposited by Schwann cells; contains sphingomyelin Nodes of Ranvier: 2–3 micrometer gaps in myelin every 1–3 mm Internode The collections of nerve cell bodies within the CNS are called nuclei, and outside the CNS ganglia.
Myelin Sheath in the Peripheral Nervous System • A protein–lipid complex wrapped around the axon • Schwann cells wrap their membranes up to 100 times • Function: • Myelin acts as an electrical insulator for the axonal core • Enhances the speed and efficiency of axonal conduction
Myelin Sheath in the Nervous System • One Schwann cell myelinates one internode in the peripheral nervous system • One Oligodendrocyte may myelinate multiple axons in central nervous system
15 Myelination of Nerve Fibers Axon invaginates the Schwann cell plasma membrane forms mesaxon Mesaxon wraps repeatedly around axon spirals form cytoplasm extruded Inner membrane layers fuse myelin sheath formed
16 Myelination of Nerve Fibers • Predominantly lipid + protein • Whitish appearance • Function: • Electrical insulation • Prevents ion flux across axon membrane • Myelin thickness: depends on number of spirals • Electron microscopy: • Major dense line (~2.5 nm): fused inner protein layers • Minor dense line (~10 nm): outer lipid layers of adjacent membranes • Each Schwann cell covers short segment → interdigitates with next Schwann cell Segmented myelin separated by nodes of Ranvier
17 Myelination of Nerve Fibers • Non-myelinated axons are also surrounded by Schwann cells • Several axons invaginate longitudinally into the Schwann cell cytoplasm • Each axon sits in a groove within the Schwann cell • Schwann cell plasma membrane fuses along groove opening, sealing the axon in an extracellular compartment • Multiple axons (up to 15+) may share one Schwann cell • Function: support and insulation without full myelin
Axonal Transport Mechanisms
Axonal Transport Mechanisms • Orthograde Transport • movement from the cell body toward axon terminals • Fast Component occurs at ~400 mm/day using the motor protein kinesin • Slow Component occurs at 0.5–10 mm/day along microtubules • Retrograde Transport • movement from nerve ending to soma at ~200 mm/day • Dynein motors carry used vesicles, growth factors, and viruses back to soma
Nerve fibre - Axon Nerve - Bundle of nerve fibres outside the CNS Tract - Bundle of nerve fibres inside the CNS
21 Structure of the Peripheral Nerve • Endoneurium: • It is a loose delicate connective tissue that surrounds the individual nerve fibres. In fact • it lies between the nerve fibres within a nerve bundle. • Perineurium: • Made up of a condensed layer of collagenous connective tissue that • surrounds the bundle of nerve fibres. • Epineurium: • Dense connective tissue sheath • Surrounds and encloses the bundles of nerve fibres forming the nerve trunk • i.e. it surrounds the entire nerve • It contains tiny blood and lymph vessels.
22 Functional classification Sensory neurons Primary sensory neurons: Secondary sensory neurons: Tertiary sensory neurons: Motor neurons Somatic nervous system Upper motor neurons Lower motor neurons Autonomic nervous system: Preganglionic neurons: Postganglionic neurons:
23 Functional classification Sensory neurons They carry impulses from the receptor organs to the CNS. Primary sensory neurons: The cell bodies lie outside the CNS Except mesencephalic nucleus of V trigeminal nerve Secondary sensory neurons: The cell bodies of these neurons lie in the CNS. Tertiary sensory neurons: The cell bodies lie in the thalamus. Motor neurons Somatic nervous system Upper motor neurons Lower motor neurons Autonomic nervous system: Preganglionic neurons: Postganglionic neurons:
24 Functional classification Sensory neurons Primary sensory neurons: Secondary sensory neurons: Tertiary sensory neurons: Motor neurons They transmit impulses from the CNS to the muscles and glands. The cell bodies of these neurons liewithin the CNS except those of postganglionic neurons of autonomic nervous system. Somatic nervous system Upper motor neurons Cell bodies located in the cerebral hemisphere synapse with the motor neurons of the cranial nerve nuclei in the brainstem and motor neurons of the spinal nerves in the anterior horns ofcthe spinal cord. Lower motor neurons Cell bodies located in the brainstem and spinal cord anterior horn. Suppl skeletal muscles Autonomic nervous system: Preganglionic neurons: Postganglionic neurons
25 Functional classification Sensory neurons Primary sensory neurons: Secondary sensory neurons: Tertiary sensory neurons: Motor neurons Somatic nervous system Upper motor neurons Lower motor neurons Autonomic nervous system: Preganglionic neurons: Cell bodies of these neurons lie in the brain and spinal cord. Postganglionic neurons: Cell bodies lie outside the CNS in lateral, collateral and terminal autonomic ganglia.
26 Nerve Classification Based on Function / Area of Innervation • Somatic Sensory Fibers • Convey impulses from skin, bones, muscles, joints → CNS • Somatic Motor Fibers • Carry impulses from CNS → skeletal muscles • Visceral Sensory Fibers • Convey impulses from visceral organs & blood vessels → CNS • Visceral Motor Fibers (Autonomic Motor) • Carry impulses from CNS → cardiac muscle, glands, smooth muscles
27 Classification of Peripheral Nerve Fibers • Based on Axonal Diameter and Conduction Velocity
Classification of Nerve Fibers
Classification of Nerve Fibers
GLIA
Glia Microglia Immune system scavenger cells Remove debris from injury, infection, or disease (e.g., MS, Alzheimer's) Arise from outside the nervous system; embryologically unrelated to neurons Macroglia Oligodendrocytes/ Schwan cells Oligodendrocytes in CNS, form myelin for many neighboring axons simultaneously Schwann cells in PNS provide myelin for a single segment of one axons Ependymal Cells Secretion of CSF Astrocytes Fibrous Astrocytes Found in white matter Structural support of nerve fibers, Involved in scar formation in response to injury End-feet support blood brain barrier Regulate concentration of ECF ions Protoplasmic Astrocytes Found in gray matter Blood-brain barrier, induces capillaries to form tight junctions via end-feet Take up excess and neurotransmitters (Glutamate, GABA) Tropic Function produce substances that support neuronal survival
Glia Microglia Immune system scavenger cells Remove debris from injury, infection, or disease (e.g., MS, Alzheimer's) Arise from outside the nervous system; embryologically unrelated to neurons Macroglia Oligodendrocytes/ Schwan cells Oligodendrocytes in CNS, form myelin for many neighboring axons simultaneously Schwann cells in PNS provide myelin for a single segment of one axons Ependymal Cells Secretion of CSF Astrocytes Fibrous Astrocytes Found in white matter Structural support of nerve fibers, Involved in scar formation in response to injury End-feet support blood brain barrier Regulate concentration of ECF ions Protoplasmic Astrocytes Found in gray matter Blood-brain barrier, induces capillaries to form tight junctions via end-feet Take up excess and neurotransmitters (Glutamate, GABA) Tropic Function produce substances that support neuronal survival Largest & Most numerous Smallest Derived from fetal monocytes Microglia: Derived from fetal monocytes (mesoderm) All other neuroglia: ectoderm
33 Glial Responses to Injury • Astrocytes • Proliferate after neuronal death • Fill spaces left by lost neurons → replacement gliosis • Clinical relevance: • Glioblastoma multiforme arises from astrocytes • Highly aggressive brain tumor, survival ~2–3 months • Microglia • Migrate to damaged CNS regions (infection, trauma, stroke) • Phagocytose necrotic tissue • Pathological relevance: • Large numbers of microglia indicate areas of CNS damage during autopsy
34
Thank You References: • Guyton, A. C., & Hall, J. E. (2021). Textbook of Medical Physiology (15th ed., Chapter 5: Membrane Potentials and Action Potentials). Philadelphia, PA: Elsevier. • Barrett, K. E., Barman, S. M., Brooks, H. L., & Yuan, J. X.-J. (2019). Ganong’s Review of Medical Physiology (26th ed., Chapter 4: Excitable Tissue: Nerve). New York, NY: McGraw-Hill Education. • Sherwood, L. (2015). Human Physiology: From Cells to Systems (9th ed., Chapter 4: Principles of Neural and Hormonal Communication ). Boston, MA: Cengage Learning.