Neurons and Glial Cells (Week 1)

Thinglink Focus Questions

1.) Why was it harder to prove the brain is made of cells than other tissues? 

• Because brain tissue is very densely packed together and too clumped up to see through

2.) Who discovered the "Black Reaction"? 

• Camillo Golgi

3.) What part(s) of cells were stained?  How many (all, most, few, none)? 

• Some brain cells (neurons) were stained

4.) What tool was invented ultimately allowing us to view the synapse separating neurons and thus prove the neuron doctrine?

• Electron microscope

5.) Who was responsible for our current understanding of the neuron doctrine? 

• Ramon Y Cajal

Dendrites and Dendritic Spines

Dendrites:

• Like the branches of a tree

• Receive chemical messages from other cells, conduct post-synaptic potentials toward the cell body

  • Potential = Electrical Events

• Receives thousands of inputs

• Arborization = Group of dendrites

Dendritic Spines:

• Small protrusion that receives input from a single axon

• Sensitive to type and amount of synaptic activity

• Shows plasticity (change in structure in a way we can measure over time)

• Characterized by shape:

Axons and Myelin Sheath

Axons: 

• Like the trunk of a tree

• Conducts electrical signals called action potentials

• Most neurons have 1 axon (vs many dendrites), but can branch to form axon collaterals

• Often has myelin sheath

  • A fatty coating that is provided by glial cells

  • Many job is to insulate the electrical signal so that there isn’t decay and the signal can reach the end

• Ends in axon terminal which releases neurotransmitters

Myelin Sheath (Insulates Axons)

• Fatty insulation made by glial cells (oligodendrocytes of schwann cells)

  • No ion channels present under sheath

• Gaps between myelination are called Nodes of Ranvier

  • Allows saltatory conduction of action potentials

    • The signal jumps from node to node

  • Many ion channels at nodes

• Myelinated neurons are always faster than unmyelinated

• Some nerve fibers don’t have myelination -> more ion channels have to be opened

Axon Variability

• Diameter:

  • More important when unmyelinated

  • Varies by species

  • Larger diameter = Less resistant, faster signal

    • Still not as fast of myelinated but faster than small diameter

  • Small diameter = More resistance, slower signal

• Length:

  • Local Circuit: (short) communicates with neurons in immediate vicinity

    • Same part of the brain

  • Projection Neurons: (very long) communicates with neurons in distant areas of the nervous system

    • A neuron that starts in spinal cord and ends in big toe

Axon Terminal

• Terminal contains mitochondria (provides ATP/energy) and synaptic vesicles containing neurotransmitters

• “Presynaptic” terminal sends chemical messages to other neurons or tissue targets

Cells Body (Soma), Cytoskeleton, Membrane

The Cell Body (Soma)

• Cytoplasm: cytosol and all organelles found in other cells

• Nucleus: contained in nuclear envelope

  • Gene expression

  • Transcription

  • mRNA assembly

  • Translation

• Provides metabolic (energy) and synthetic (protein) support

• Acts like a “gate” for information flow to and from other neurons

• Receives and integrates signals from many sources of input (integration zone)

Red = Inhibitory synapse (not to fire)

Green = Excitatory synapse (to fire)

Neurocytoskeleton Fibers

• Microtubules: responsible for transport of neurotransmitters and other cellular products to (retrograde transport) and from (anterograde transport) the cell body

  • Anterograde (forward acting): Cell body to axon terminal

  • Retrograde (backward acting): Axon terminal to cell body

• Neurofilaments: structural support to axon

• Microfilaments: reorganization of neuronal branches

Neural Membrane

• Defines intracellular (inside cell) /extracellular (outside cell) boundaries

• Made of phospholipid bilayer 

• Contains protein molecules, receptors, channels/Pumps

• Selectively permeable -> proteins will allow some things through but not others

  • Allows polarization

Classification of Neurons

*About 86 billion neurons in the brain -> Typically not evenly spread out in the brain

*About 86 billion glial cells in the brain

Structural Classification

• Bipolar:

  • Two processes separated by cell body

  • Often sensory

• Pseudounipolar: single elongated process with cell body off to side

  • Less common more sensory functions

• Multipolar:

  • Many dendrites and a single axon

  • Most common

Functional Classification

• Sensory: to brain to spinal cord (afferent)

• Motor: from brain and spinal cord to muscles and organs (efferent) 

• Interneuron: connects to one neuron to another in brain or spinal cord

  • Local = short distance; Projection = long distance

• Neuroendocrine: secretes chemicals into bloodstream

Glial Cells

Glial Cells in General

• Non-neural (no Action Potentials)

• Physical and functional support functions to neurons

Astrocytes

• Appearance of a star

• Most common glia

• Two types:

  • Fibrous: long and slender with less branches; found in white matter

  • Protoplasmic: thick projections with many branches; found in gray matter

Astrocyte Functions

• Form structural matrix for neurons

• Contribute to Blood Brain Barrier

  • Transfer nutrients to neurons, block some circulating toxins from accessing neural tissue

  • Blood Brain Barrier: A barrier to the transfer of molecules from the circulation into the brain formed by the astrocytes (block germs and bacteria)

• Regulate chemicals around neurons

  • Form tripartite synapse and participate in isolation and uptake

• After injury: form scar tissue that inhibits regrowth and connectivity

Oligodendrocytes and Schwann Cells

• Both involved in myelination around axons

  • Improves signal and insulation

• Oligodendrocytes (Central NS): one cell myelination ~ 15 axons

  • Central NS = brain and spinal cord

• Schwann Cells (Peripheral NS); myelinate a single axon segment

  • Peripheral NS = Everywhere by brain and spinal cord

• Damage associated with multiple sclerosis 

Ependymal Cells

• Found in membrane lining ventricles and central canal of spinal cord

• Secrete liquid called cerebrospinal fluid (CSF)

• Involved in Blood Brain Barrier

Radial Glia

• A type of stem cell that can create other cells

• Proliferative

  • Neural and Glial progenitors

• Structural scaffold during early neurodevelopment

  • Provide long rope-like fibers that guide young brain cells into place as your brain forms

Microglia

• All of the others above are macroglia

• Sense molecules associated with cellular damage and phagocytose (digest) the debris

• 10-15% of all cell in brain

• First and main form of active immune defense in CNS

  • Immune cells

• Activated by inflammation

  • Too much activation can cause them to start attacking healthy neurons

• Destroy infectious/toxic agents

• Antigen presentation -> Like a recognition flag, so they can mount their defense sooner for other microglias

• In Alzheimer’s disease microglia are hyperactivated and cause too much inflammation

Application to Health

1.)  As the motor neurons stop sending signals, what happens to the muscles? (paralysis or contraction)

• The muscles weaken and paralysis occurs

2.) In ALS patients, what is happening to proteins in the cell body? 

• The proteins that don’t pass to the nucleus build up in the cytoplasm, mis fold and aggregate, and then the build up which leads to toxicity to other cells

3.) What can mitochondrial damage lead to? 

• It can lead to oxidative stress which can break parts of the dna and impaired repairs

4.) What happens if vesicles cannot be released? 

• The neuron won’t be able to send a signal

5.) Which glial cells were mentioned as "not working" in ALS?  Which glial cells were associated with "damaging factors"? 

• Oligodendrocytes do not work in ALS patients

• Astrocytes and microglia are associated with damaging factors