Module 1.5: Nervous Tissue Dr. Darren Hoffmann Lecture Objectives: After this lecture, the student will be able to: 1) Define what makes nervous tissue unique 2) Diagram the different forms of neurons 3) Describe the cellular specializations of neurons and correlate with their histological appearance 4) Name the proteins required for anterograde and retrograde transport along an axon 5) Identify the proteins required for maintaining neuron membrane potential 6) List the sequence of cellular events in transmitting an action potential 7) Predict the effect of inhibiting Na+ channels in neurons 8) List the sequence of cellular events in a chemical synapse 9) Distinguish between an electrical and chemical synapse 10) Name the different glial cells and describe their basic functions 11) Draw a myelinated axon with its associated myelinating cell 12) Differentiate between unmyelinated neurons in the PNS and CNS 13) Visually distinguish histological sections of Dorsal Root (sensory) vs. Sympathetic ganglia 14) Identify the connective tissues of a peripheral nerve in cross section or long section 15) Explain how nerve regeneration and neural plasticity occur 16) Interpret the name of a nervous system tumor to identify the cells of origin for the tumor Lecture Outline: Part A: General Organization of Nervous Tissue and Neurons A1. Introduction and key properties of nervous tissue Nervous tissue is: - composed of neurons and glial cells - excitable, chemically and electrically - utilizes action potentials to transmit signals - stabilizes internal conditions in the body - facilitates the body’s interaction with the environment - develop from embryonic ectoderm Hoffmann; Nervous Tissue; Page 1 A2. Types of Neuron i. Multipolar Motor Neurons CNS → Multiple dendrites → Cell Body → Axon → Effector tissue ii. Pseudounipolar Sensory Neurons (General Sensation) Peripheral signal → Dendrite → Cell Body → Axon → CNS iii. Bipolar Sensory Neurons (Special Sensation) Peripheral signal → Dendrites → Cell Body → Axon → CNS A3. Cellular specializations of neurons i. Cell Body (Soma) - Main center for protein synthesis - Can receive synapses - Large pale nucleus w/ prominent nucleolus Pale because chromatin is highly dispersed Lots of transcription occurring – HIGH synthetic activity ii. Other organelles - LOTS of rER and free ribosomes (Nissl bodies) rER: vesicle proteins Free ribosomes: structural proteins - Golgi Only in cell body, perinuclear - Mitochondria Throughout cell Abundant in nerve terminals - Cytoskeleton Microtubules Vesicle highway Neurofilaments (intermediate filaments) Control axonal diameter Hoffmann; Nervous Tissue; Page 2 iii. Dendrites (Tree-like branches) - Branching pattern: become thinner as they subdivide - Similar cytoplasmic contents as soma, minus Golgi - Dendritic plasticity Learning/memory induce actin-mediated dendritic changes More dendritic branching New and larger Dendritic spines (Receiving ends of synapses) iv. Axons (Single long branches) - Axolemma (plasma membrane of axon) - Axoplasm (cytoplasm of axon) - Originate from Axon Hillock - Initial segment – Pre myelin sheath Site of summation of excitatory and inhibitory signals Determines if an action potential will occur - No ER or Ribosomes in Axon Requires vesicle transport up and down axon microtubules A4. Axonal Transport Anterograde Flow (Kinesin protein) Slow (2-3 mm/day) Structural proteins and microfilaments Intermediate Mitochondria Fast (50-400 mm/day) Vesicles and synaptic proteins Retrograde Flow (Dynein protein) Endocytosed substances going back to Cell body Pathogens can use these transport mechanisms! *Herpes simplex virus uses anterograde mechanisms to travel from Dorsal Root Ganglion to skin surface *Rabies virus uses retrograde mechanisms to get from the skin to the central nervous system Hoffmann; Nervous Tissue; Page 3 Part B: Key Functions of Neurons B1. Membrane Potential Membrane Potential: The purposeful electrochemical gradient of ions across the membrane (in this case, axolemma) Action Potential: Rapid rise and fall of membrane potential in a cell, along a consistent trajectory Requires: Ion pumps and channels along the length of the neuron Voltage-gated Sodium channels Voltage-gated Potassium channels Na+/K+ pumps High extracellular Na+ (15 mM intracellular, 150 mM extracellular) High intracellular K+ (150 mM intracellular, 5 mM extracellular) Resting membrane potential of a neuron: -65mV *Important: Na+/K+ pump must be constantly working to restore correct levels of Na+ outside and K+ inside. This is active transport and requires ATP. Clinical Correlation: ALL local anesthetics are membrane-stabilizing drugs! Most act by inhibiting Na+ influx through Na+ channels Receptor site is thought to be on the cytoplasmic side Hoffmann; Nervous Tissue; Page 4 B2. Synaptic Communication Synapse: Transmission of a chemical or electrical signal from one cell to another i. Electrical synapses: Formed by gap junctions between adjacent cells ii. Chemical synapses: Formed by vesicles which transport chemicals between adjacent cells Chemical Synapses Require: Presynaptic cell: Neurotransmitters (small peptides/amino acids/amines and other chemicals) Exocytosis processes (to release vesicle-bound transmitters into synaptic cleft) Endocytosis processes (to recycle transmitters back into the cell) Post-synaptic cell: Receptors for the transmitters Sequence of Synaptic Transmission 1. Axon depolarization (see action potential above) 2. Ca++ influx at nerve terminal 3. Exocytosis of Neurotransmitter-containing vesicles 4. Release of Neurotransmitters into synaptic cleft 5. Neurotransmitter binding to receptors on post- synaptic cell 6. Depolarization of post-synaptic neuron 7. Membrane retrieval and reabsorption of neurotransmitters What happens to neurotransmitters? -Enzymatic breakdown (Cholinesterase from Muscle lecture) -Diffusion -Endocytosis Hoffmann; Nervous Tissue; Page 5 Part C: Glial Cells C1. General Structure & Function of Glial cells Glial cells are 10X more abundant than neurons! Types of glial cells i. Metabolic support cells (Astrocytes, Satellite cells) ii. Lining cells (Ependymal cells) iii. Phagocytic cells (Microglia) iv. Myelinating cells (Oligodendrocytes, Schwann cells) C2. Metabolic support cells • Metabolic support (Astrocytes-CNS; Satellite cells-PNS) Most numerous glial cells Form cellular scar tissue in injury to nervous tissue Control/regulate extracellular environment of nervous tissue Release metabolic compounds (transport energy/lactate to neurons) and transfer molecules/ions to neurons Absorb local excess neurotransmitters Interconnected to each other through gap junctions Processes surround vessels to form the blood-brain barrier C3. Lining cells and Phagocytic cells • Lining cells (Ependymal Cells) Lining cells of the ventricles of brain/spinal cord Ciliated cells - cilia move to circulate cerebrospinal fluid • Phagocytic cells (Microglia) Smallest glial cell (hence 'micro') Two different cellular forms: - Resting: tiny flat nuclei with lots of branching - Activated: retract their process and become phagocytic macrophages Hoffmann; Nervous Tissue; Page 6 C4. Myelinating Cells (Schwann cells - PNS and Oligodendrocytes - CNS) Myelination – Why have it? It insulates axons, allows for accelerated electrical conduction along axon The truth about “unmyelinated” axons In CNS, unmyelinated axons are in fact, bare axons In PNS, unmyelinated axons are grouped multiply within a Schwann cell, but the cell is not wrapped around the axons multiple times as in myelinated axons Unmyelinated Myelinated • Oligodendrocytes – Myelinating cells in CNS Each Oligodendrocyte has several branches which can envelop segments of multiple axons • Schwann Cells – Myelinating cells in PNS Each Schwann cell forms one internode on one axon Gaps are called nodes of Ranvier Hoffmann; Nervous Tissue; Page 7 Part D: Histological Organization of Nervous Tissue Neurons group together such that axons run with axons and cell bodies are housed with cell bodies Terminology: PNS CNS A group of neuron cell bodies Ganglion Nucleus A group of axons Nerve Tract D1. Ganglia i. Sympathetic ganglia - Less neurons per unit area (Neurons are dispersed throughout ganglion) - Neurons often display eccentric (off-center) nuclei ii. Sensory ganglia - Many more neurons per unit area (cell bodies are larger, more numerous, more packed together, and separated from the large axon bundles passing through) - Neurons often display central nuclei Both types of ganglia have: Satellite cells studding the surface of the neuron cell bodies Sensory Ganglion Sympathetic Ganglion Hoffmann; Nervous Tissue; Page 8 D2. Peripheral nerves Connective Tissues are used to bundle nerves together similar to muscle Epineurium (around the entire nerve) Perineurium (around a group of axons) Endoneurium (around a single axon) *These connective tissues can be seen in cross sections through nerves *The myelin sheath and endoneurium can be seen in longitudinal sections through nerves Hoffmann; Nervous Tissue; Page 9 Part E: Regeneration, Plasticity and Tumors E1. Regeneration, Placticity and Tumors -Neurons CAN regrow, as long as cell body isn’t destroyed -Neurons are terminally differentiated, so they can’t replenish themselves via mitosis -Glial cells CAN replenish themselves through mitosis i. Regeneration: repair of a damaged nerve/neuron -Regrowth of an axon requires the presence of the endoneurium of the distal end of the axon -Myelin sheath and distal axon degenerate, but endoneurium provides a pathway