Cell Biology of Neurons
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Transcript of Cell Biology of Neurons
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Cell Biology of Neurons
Sept 8, 2006
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The nervous system is composed of billions of processing units (neurons) whose cellular processes (the dendrites and axons) form an elaborate and complex meshwork of circuits and pathways. Signals are transmitted between neurons via specialized cell-cell contacts known as synapses.
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Neuronsare highly
compartmentalizedcells
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Neuronsare highly
compartmentalizedcells
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Neuronsare highly
compartmentalizedcells
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Neuronal form is highly variable
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The Neuronal Cell Body
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Neuronal cell bodies:-typical assortment of organelles-point of origin for processes-transcriptional powerhouses-provide virtually all of the protein
constituents for the entire cell
100 µm toe
6 feet
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Rough endoplasmic reticulum
Lysosome
Mitochondrion
Ribosomes
Golgi complex
Cytosol
Peroxisome
Smooth endoplasmic reticulum
Plasma membrane
Nucleus
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The plasma membrane bounds the cell, separating the ECF from the ICF.
• It controls the passage of substances into and out of the cell.
The nucleus contains DNA and specialized proteins enclosed by a double-layered membrane.
• DNA codes for the synthesis of structural and enzymatic proteins, and is the blueprint for cell replication.
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The cytoplasm consists of the organelles and the cytosol.
• Organelles are separate, membrane-bound compartments. Organelles include the: endoplasmic reticulum Golgi complex lysosome peroxisome mitochondrion
• The cytosol is a semiliquid, gel-like mass.
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Smooth ERRough ER
Ribosomes
ER lumen
•The rER is an extensive, continuous membranous network of fluid-filled tubules and flattened sacs that is partially covered with ribosomes. rER synthesizes proteins for secretion and membrane construction.
•The sER packages new proteins in transport vesicles.
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The Golgi complex packages vesicles and targets them to the appropriate
cellular destination.
• Set of stacked, flattened membranous sacs. It modifies, packages, and distributes products.
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Peroxisomes and Lysosomes
Peroxisomes house oxidative enzymes that detoxify various
waste products.
• Lysosomes serve as the intracellular digestive system. They are membranous sacs containing hydrolytic enzymes that destroy foreign substances and cellular debris.
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Mitochondria are the energy organelles. They are enclosed by a double membrane. The inner
membrane is folded into cristae.
• Mitochondria are the major site of ATP production. They contain enzymes for the citric acid cycle (matrix) and the electron transport chain (inner membrane cristae).
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The Cytosol functions for intermediary metabolism, protein synthesis, and
nutrient storage.• Enzymes in the cytosol regulate degradation, synthesis
and transformation of small organic molecules (simple sugars, amino acids, fatty acids), capturing energy for cellular activities and raw materials for maintenance of cellular structure, function and growth.
• Ribosomes (free in the cytosol) are the site of protein synthesis.
• Glycogen and fat are stored in the cytosol (inclusion bodies).
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The axon hillock and initial segment
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The Myelin Sheath
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The Axon
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Axonal arborizations can be quite complex
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The Synapse
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Symmetric and
asymmetric synapses
Dend
sp
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Dynamic Polarization
Axo-dendritic
Axo-somatic
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Dynamic Polarization: Exceptions
Axo-axonic
Spinal cord afferent terminals contacted by interneurons-
“pre-synaptic inhibition”
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Dynamic Polarization: Exceptions
Dendro-dendritic
Dendro-somatic
Olfactory bulb and retina
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Dendritic arbors: complex geometries
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The DendriteT.E.M. Freeze fracture
sp
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Polyribosomes are sometimes associated with dendritic spines
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Spine morphology is affected bysynaptic activity
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The Cytoskeleton
(Intermediate filaments) Abnormalities associated with degenerative
diseases - Alzheimers, Down’s, ALS, etc.
Intracellular “rapid” transport - severely disrupted by Colchicine (depolymerize microtubules
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The Cytoskeleton is a complex protein network in the cytosol.
• The cytoskeleton functions as an integrated whole and links other parts of the cell together.
• Its three types of elements are microtubules, microfilaments, and intermediate filaments.
neurofilaments
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Axoplasmic transportDendrites have limited capabilities for local protein synthesis,
but axons have essentially noneThus, both types of processes require transport of proteins
produced in the cell bodyMultiple transport systems, transport different types of material
to different intracellular compartments, at different rates
Component Substances carried Rate
“Slow” axonal transport Cytoskeletal proteins ~ 1-2 mm / day Anterograde SCa Tubulin Anterograde SCb Actin, neurofilaments
“Rapid Transport” Membranous organellespreferentially to synaptic terminals
400 mm / day
Anterograde Vesicles, mitochondria fastest Retrograde Lysosomes, enzymes 200-300 mm /day
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Cell body
Endoplasmicreticulum
Nucleus
Lysosome
Golgicomplex
Microtubular “highway”
Axon Debris
Secretoryvesicle
Axonterminal
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Neurocytology & Tract-tracing
Widely used techniques for studying neurons and circuits:
Visualization of neurons Nissl staining, Golgi methods, intracellular dye injections, immunohistochemistry
Degeneration and reactive changes in the neuron after lesion
Wallerian degeneration
Axonal transport methods
Autoradiography, HRP, Lectins, Biocytin, Dextrans, Fluorescent Tracers
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Neuronal cell bodies: Nissl method
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The Golgi method
cerebellarPurkinje cell
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Intracellular injectionof Lucifer Yellow
Biolistics (“gene-gun”)
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Immunohistochemistry
PEP-19 antiserum reveals the calyx of Held
L7 protein reveals cerebellar Purkinje cells
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Tract-Tracing
Anterograde Degeneration:
Reduced silver method
and electron microscopy
Anterograde Walleriandegeneration
Retrogradedegeneration
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AnterogradeTract-tracing Autoradiography
Anterogradetransport
Uptake by Cell body
Collateralprojections
Labeledterminals
Radioactively labeled amino acid
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RetrogradeTract-Tracing HRP, Dextran
Retrogradetransport
HRP
Uptake by terminals
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Tract-tracing:
Fluorescent tracers
Superiorolivaryneuron
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Combining techniques at the LM and EM level