cell biology of neurons sept 8, 2006. the nervous system is composed of billions of processing units...

Cell Biology of Neurons

Sept 8, 2006

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.

Neuronsare highly

compartmentalizedcells

Neuronsare highly

compartmentalizedcells

Neuronsare highly

compartmentalizedcells

Neuronal form is highly variable

The Neuronal Cell Body

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

Rough endoplasmic reticulum

Lysosome

Mitochondrion

Ribosomes

Golgi complex

Cytosol

Peroxisome

Smooth endoplasmic reticulum

Plasma membrane

Nucleus

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.

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.

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.

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.

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.

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).

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).

The axon hillock and initial segment

The Myelin Sheath

The Axon

Axonal arborizations can be quite complex

The Synapse

Symmetric and

asymmetric synapses

Dend

sp

Dynamic Polarization

Axo-dendritic

Axo-somatic

Dynamic Polarization: Exceptions

Axo-axonic

Spinal cord afferent terminals contacted by interneurons-

“pre-synaptic inhibition”

Dynamic Polarization: Exceptions

Dendro-dendritic

Dendro-somatic

Olfactory bulb and retina

Dendritic arbors: complex geometries

The DendriteT.E.M. Freeze fracture

sp

Polyribosomes are sometimes associated with dendritic spines

Spine morphology is affected bysynaptic activity

The Cytoskeleton

(Intermediate filaments) Abnormalities associated with degenerative

diseases - Alzheimers, Down’s, ALS, etc.

Intracellular “rapid” transport - severely disrupted by Colchicine (depolymerize microtubules

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

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

Cell body

Endoplasmicreticulum

Nucleus

Lysosome

Golgicomplex

Microtubular “highway”

Axon Debris

Secretoryvesicle

Axonterminal

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

Neuronal cell bodies: Nissl method

The Golgi method

cerebellarPurkinje cell

Intracellular injectionof Lucifer Yellow

Biolistics (“gene-gun”)

Immunohistochemistry

PEP-19 antiserum reveals the calyx of Held

L7 protein reveals cerebellar Purkinje cells

Tract-Tracing

Anterograde Degeneration:

Reduced silver method

and electron microscopy

Anterograde Walleriandegeneration

Retrogradedegeneration

AnterogradeTract-tracing Autoradiography

Anterogradetransport

Uptake by Cell body

Collateralprojections

Labeledterminals

Radioactively labeled amino acid

RetrogradeTract-Tracing HRP, Dextran

Retrogradetransport

HRP

Uptake by terminals

Tract-tracing:

Fluorescent tracers

Superiorolivaryneuron

Combining techniques at the LM and EM level