cellular organization of the nervous system

principal cells of the nervous system

• neuron

• glia = “glue”

  • outnumber neurons 10:1

glial cells of CNS

• microglia

• astrocytes

• oligodendrocytes

• ependymal cells

microglia

• smallest glial cell

• immune response in brain

  • destroy microorganisms

  • clear debris

  • promote tissue repair

  • scavenge for damaged neurons and protein plaques

  • clear old synapses —> get rid of what’s not useful

astrocytes

• primary support cell for neuron

• regulates the chemical content of extracellular space (ions, Na+, K+)

• direct role in cell signaling (can communicate)

• end feet that connect neurons and capillaries

  • blood brain barrier

• major role in response to CNS injury

  • glial scar —> astrocytes create around damaged area

oligodendrocytes

• myelin producing

  • proteins and fats that surround neurons

  • provide metabolic support to axon

  • speed communication through axon

ependymal cells

• line ventricles to form the choroid plexus

  • choroid plexus - produces and circulates CSF

• regulate ionic concentration

glial cells of PNS

• Schwann cells

• satellite cells

Schwann cells

• myelinating glia of PNS

  • provide metabolic support and speed communication through axon

• connective tissue scaffold

  • development

  • repair

satellite cells

• found primarily in ganglia - structural support for nodes in ganglia

  • provide nutrients and control environment around neuron

  • collection of neural cell bodies in the PNS

myelin in CNS vs PNS

• terminology

  • node of ranvier - spaces between internodes

  • internode

• oligodendrocytes

  • CNS myelin formation

  • 1 oligo cell to multiple internodes

• Schwann cells

  • PNS

  • 1 Schwann cell to 1 internode

  • the PNS better supports axon regeneration

multiple sclerosis

• CNS demyelinating diseases

• chronic autoimmune disease

  • inflammation

  • demyelination

  • gliosis —> damage to glia

  • neuronal loss

• major processes

  • inflammation resulting in plaques and injury to BBB

  • neurodegeneration

    • axons, neurons, synapses

• myelin regulates axon —> fairly damaging

guillain barre syndrome

• PNS

• immune mediated neuropathy

• destruction of Schwann cells and neurons

  • flaccid paralysis (proximal to distal)

  • life threatening (respiratory function)

neurons structure & function

• structure

  • cell body (integration)

  • dendrites

    • short

    • receive information

  • axons

    • long

    • conduct information

  • axon terminal

    • synaptic bouton

• function

  • reception

  • integration

  • transmission and transfer

gray matter vs white matter

gray matter

• where cell bodies live

• this is where synapses are (processing occurs here)

  • group of functionally connected neurons are called

    • ganglia (PNS)

    • nuclei (CNS)

white matter

• myelinated

• bundles of axons

• conduct and send signals to gray matter

• functionally connected neurons called:

  • fasciculus, funiculus, lemniscus, peduncle and tract (all mean white matter)

electrical and chemical signals

electrical = action potential

chemical = neurotransmitter

• dendrites and cell bodies receive info

• transmitted down axon as electrical signal

• at synapse, electrical signals cause release of chemical messenger into the synapse

• chemical messenger is received by post synaptic dendrite and converted into electrical signals

resting

membrane potential

the difference in the electrical charges inside and outside the cell create an electric potential

• -65mV

  • steady state, no net flow of ions

• metabolic energy is expended to maintain this gradient (difference)

  • Na+/K+ pump

ions cross membrane through channels

• modality gated - photoreceptors, mechanoreceptors, thermoreceptors

• ligand gated

  • direct:

    • NT binds and directly opens the channel

    • faster but effects are local

  • indirect

    • NT binds and through a second messenger system that will bind and open the channel

    • G protein coupled receptors are most common

    • slower but more widespread effects

• voltage gated

  • change in electric potential

action potential

• momentary change in the electrical gradient across cellular membrane

• creates an electrical signal that can move down the axon —> propagate

• “all or nothing” —> if the change in the membrane is sufficient an action potential will be generated

action potential coded

• stimulus applied —>

• difference in Na+ inside/outside cell causes Na+ to rush into cell —> this makes inside of cell less negative (depolarization)

  • if threshold change is -15mV (an AP is generated)

• absolute refractory

  • no amount of additional stimuli can elicit another AP

• as potential ascends to 0mV —> Na+ gates close and K+ open —> K+ enters to restore resting membrane potential

• relative refractory period

  • K+ channels stay open

  • more polarized

  • return to RMP

local potential

• not enough to stimulate AP

• small changes in membrane potential

  • do not reach threshold

• can be summated

  • spatial - multiple axons acting on another axon (same geographic area)

  • temporal - over the course of time

changes in potential can make it…

• MORE likely for AP to fire

  • depolarized

  • excitatory post synaptic potential (EPSP) —> Na+

• LESS likely for AP

  • hyperpolarized

  • inhibitory post synaptic potential (IPSP) —> chlorine (Cl-) channels open instead of Na+

structural adaptations to speed up AP

• myelin

  • nodes of ranvier contain dense cluster of Na+ channels

  • saltatory conduction —> myelin allows signal to jump from node to node

• diameter —> reduces resistance to charge (fatter axons = fast)

synaptic terminal events

• AP arrives at axon terminal —> activates voltage gates (Ca+ channels)

  • Ca+ enters the cell

• Ca+ activates vesicle binding

  • brings vesicles filled with neurotransmitters to membrane

  • NT released into synaptic cleft

• NT diffuse across membrane

• NT bind to receptors in post synaptic membrane

  • if ESPS —> increase Na+

  • if ISPS —> increase Cl-

• removal of NT from synapse

  • broken down with enzymes

  • simple diffusion

  • reuptake into presynaptic terminal

anterograde

• NT from cell body —> towards axon terminal

• kinesin

retrograde

• NT in axon terminal —> towards cell body

• dynein

botulinum toxin

• blocks action at the neuromuscular junction

• prevents release of acetylcholine (ACh) from the LMN to muscle cell

  • ACh is primary NT at NMJ

  • botox to brachialis —> block release of NT from musculocutaneous nerve

• treatment for spasticity

• paralyzes face muscles - blocks activity of NT binding to synaptic membrane

retrograde transport is a mechanism for…

pathogen entry

• herpes encephalitis

• rabies

• tetanus

diseases at NMJ

• primary symptom = weakness

• myasthenia gravis

  • disease of receptor

  • autoimmune disease that attacks ACh receptors

  • treated with drug that blocks Ach esterase (role is to break down ACh)

• Lambert Eaton Syndrome

  • autoimmune disease that attacks Ca+ channels

    • results in reduced ACh release into MJ = weaker muscle contractions

  • if ACh can hang out in cleft longer —> better muscle contraction

wallerian degeneration

• when the axon is injured, glial cells remove the damaged areas

• axon stump recedes in preparation for signal to regenerate

• cell body prepares for regrowth

  • chromatolysis

nervous system response to injury

PNS response to injury

• recovery depends on the extent of damage

• if some connective tissue remains

  • Schwann cells can scaffold and direct the regeneration to the target recovery

  • 1:1 ratio —> produce substances to support axon growth

• if axon completely severed

  • no scaffolding for regeneration

  • recovery is not expected without surgery

CNS response to injury

• very dependent on body’s practice

• after injury —> damaged area is walled off

  • microglia clear debris

  • astrocytes create physical wall around area

    • glial scar —> secretes substances that prevent axons from moving past

  • oligodendrocytes

    • many oligo:node so don’t have scaffolding abilities of PNS

    • secrete protein Nogo that limits sprouting —> prevents regeneration

      • this protein is useful in development of circuits to maintain order of tracts

      • not helpful after injury

• the CNS can reorganize —> plasticity

  • uninjured axons and dendrites can extend to other territories

  • take on damaged axon’s roles