3. Cells and Neurons

Glia in the PNS

-*Schwann cell*: Major support cell in PNS; Performs same functions as glial cells in CNS: • Produces myelin • Aids in neural recovery • Structural support - Surrounds myelinated and unmyelinated neurons in PNS to separate from extracellular environment -*Satellite cell*: provides structural support of neuron cell bodies in PNS

Types of Neurons

-*multipolar* - many poles/dendrites, one axon -shape of most nerves in CNS, most numerous -*bipolar* - one pole for dendrite, one for axon, dendrite and axon will branch, but 2 poles - cells of retina and inner ear take this shape -*unipolar* - only one projection off of cell body, divides into dendrite and axon, with branching at distal ends - found in spinal (dorsal) roots

Important Neurotransmitters

-Acetylcholine -Dopamine -Norepinephrine -Serotonin -Glutamate -GABA

Multiple sclerosis

-CNS • Autoimmune condition, onset 30-40 years, females two times as likely as males • Antibodies attack CNS myelin - myelin degenerates but initially spares axon • Glial proliferation and myelin debris contribute to plaque formulation in CNS • Plaques may cause axon to degenerate - more severe, progressive disability • Relapse-remit pattern (not with all patients), variable symptoms • No cure, treatment with corticosteroids, anti-inflammatories, other pharmaceuticals

Guillain-Barre syndrome

-PNS • Peripheral myelin—demyelinating auto-immune condition—recoverable! • Slows speed of nerve conduction • Ascending deficits in sensorineural info • Think about the news: this condition is associated with what virus? - Zika virus -goal is to keep body alive in vegetative state while recovering -mind is fine, but body "traps" people, slow steady progress -broad spectrum of impairment -drugs can speed recovery, plasmapheresis, steroids, etc. but a lot wait and see -can affect immune system, can cause relapse -can affect any age

Injury to Neurons (CNS + PNS)

-Several days following injury, if motor axon/tract/nerve not receiving input, muscles are de-enervated; continued atrophy and degeneration for months following

Alzheimer's disease

-deficienicy in cholanergic connections - hypothesis

Myasthenia gravis

-progressive motor disorder - progressive fatigue, muscle weakness, improves with rest, worsens with exercise -can be non-progressive - better outcomes

Neuron Structure - Synapse

-signal detected by dendrite, causes change in voltage of cell, received by axon hillock, if signal is large enough, axon hillock will tell axon to open membrane - action potential -if continues to endings will release neurotransmitter that will be detected by postsynaptic receptor area • Terminal boutons: release neurotransmitter from end of axon to surface of nearby neurons' dendrites across synapse • NT stimulates receptor site of next nerve cell •synapse includes knob/button/bouton, synaptic cleft, receptive site of connecting cell -some neurotransmitters are excitatory, some are inhibitory, both are normal functions

Unique to PNS

• *Endoneurium* (endoneurial membranes): -Fibrous connective tissue covering for axons -Holds together peripheral nerve fibers and surrounds nerves individually -Bundles of endoneuria are encased in perineurium -May facilitate neural recovery in PNS -Not in CNS—may be related to lack of regenerative growth in CNS (cutting-edge research may change this; not natural tho - with flood of fluid)

Neuron Structure - Soma

• *Nucleus*: command center; contains DNA, nucleolus (with RNA, ribosomal assembly) • *Cytoplasm*: aqueous/jelly-like substance within cell membrane - *Contains organelles (mitochondria, ribosomes, lysosomes, rough and smooth endoplasmic reticulum, Golgi apparatus*); Used to process, metabolize protein; Proteins sent through cell in network of microtubules

Norepinephrine

• A primary neurotransmitter in PNS: fight or flight • In CNS: in pons and medulla—paradoxical sleep (asleep but brain looks awake), random eye movement, attention

Absolute refractory period

• After the action potential, period of time where another AP cannot activate until cell returns to resting state. -axon is in hyperpolarization

Neuron Structure - Dendrites

• Cytoplasmic extension from cell body • Most numerous neuronal process • Afferent (receptive of signals) • Signal moves cell body towards the cell body • Arborization - -branching of dendrite -want dendrite to extend/connect to many different cells; -communicate/synapse with axons of neighboring cells

Neuron

• Elements: • *Cell body a.k.a. soma* - contains nucleus; filled with cytoplasm • *Dendrites* - cytoplasmic projections off of cell body • *Axon*- single long projection off of cell body. Starts at *hillock*, branches at distal end

Glutamate

• Excitatory neurotransmitter in CNS and mediates fast synaptic transmission

Excitability and Impulse Conduction

• Excitatory postsynaptic potential (EPSP) - Goal is for NT to make cell reach threshold (i.e., make cell interior less negative) - action potential • Inhibitory postsynaptic potential (IPSP) - Goal is for NT to make cell less able to fire action potential (i.e., make cell interior more negative) - cease transmission • Impulse conduction - Faster in myelinated axons (saltatory conduction); Larger diameter of axon higher velocity of impulse conduction

Ependymal Cells

• Form inner surface of ventricles • Contribute to composition of choroid plexus (which is involved in CSF production) -help CNS to avoid diffusing?

Serotonin

• In CNS and PNS • Levels vary with sleep/wake cycle • Associated with arousal, contributes to pain-control system • Associated with depression -SSRIs - allow serotonin to be released for a longer period of time

Depolarization

• Interior of cell is usually negatively charged • To generate impulse, must depolarize (reverse the polarity) the cell to trigger an action potential -Neuron's Na+ membrane channels open with an impulse large enough to reach threshold (minimum change of +10 mV) - Threshold is all or nothing—need impulse to reach threshold to activate AP; Many subthreshold impulses at same time can also activate AP -Allows Na+ ions to flow INTO cell -Causes interior of cell to become less negatively charged (depolarized) -This must occur at each node of Ranvier to propagate signal to terminal endings • Now, interior of cell is more positively charged with respect to exterior environment

Impulse Transmission: General Points

• Ions move through protein channels in axon membrane. • Synaptic knobs/terminal boutons release NT into synaptic cleft. • ONLY NT crosses synapse—not the impulse itself. • Electrochemical transmission • NT causes postsynaptic receptor to open or close its ion channel. -transmitted by neurons -at first, potassium K+ inside axon, when voltage is high enough - crosses threshold- *polarization* - sodium Na+ channels open and sodium comes in. =*Depolarization* -When reaches action potential, potassium leaves axon - *repolarization* -then in absolute refractory period-*hyperpolarization*- sodium is pumped out and potassium back in.....to get axon back to resting state -big picture: action potential but know what happens in all phases

Myelin Sheath

• Lipid material • Covers and insulates nerve fibers • Produced by oligodendroglia in CNS and Schwann cells in PNS • Forms segments separated by nodes of Ranvier • Acts as insulator of axon • Facilitates speed of nerve conduction • Saltatory conduction: propagation of signal through depolarization at each node of Ranvier • Myelin insulates signal so the charge at each node is enough to depolarize the following segment/node to propagate the signal toward the terminal boutons -in order to cross, signal has to be large enough to initiative action potential -at each node, some energy is lost

GABA

• Major neurotransmitter for CNS • Inhibitory • Implicated in Huntington's disease/chorea • Causes elevated ratio of dopamine to acetylcholine • Reduction of GABA produces abnormal movement

Oligodendroglia

• Myelinate neurons in CNS • One oligodendrocyte can myelinate several axons • Insulates and speeds up action potential conduction -Wrap around segments of axons -like insulation wrapped around an electrical wire -if lost, signal doesn't travel well thru cell

Repolarization/Falling Phase

• Na+ channels close (no more inward flux of Na+) • K+ channels now open (K+ flows out of cell) d/t cell reaching high electrical charge • Repolarization (going back to negative inside and positive outside) will result in undershoot (extensively negative state): Hyperpolarization, or cell interior becoming extremely negative, ~-80 mV • After that, K+ channels close (no more outward flow of K+) • But: need to get back to resting potential (-70 mV) • Na+ ions are pumped out (three of them) and K+ ions are pumped back in (two of them) via sodium-potassium pumps. • These pumps are working continuously throughout the process from rest to depolarization to repolarization.

Acetylcholine

• Primary neurotransmitter in PNS -In PNS: controls voluntary movement of spinal and cranial nerves -Implications - Myasthenia gravis • Also in CNS: forebrain and reticular formation -Implications - Alzheimer's disease

Dopamine

• Produced by substantia nigra cells in midbrain and project ipsilaterally to basal ganglia structures • Degeneration of substantia nigra reduces dopamine production (associated with Parkinson's disease) • Projections to cortex involved in cognition • Excessive dopamine in forebrain associated with schizophrenia • Drug abuse

Nerve Cell at Rest

• Resting membrane potential • Positive and negative ions unequally distributed on each side of membrane • Usually inside around -65 to -70 mV • More K+ inside and Na+ outside • Membrane channels "gated" by electric potential and neurotransmitter

Injury to Neurons in PNS

• Schwann cells proliferate • Form column of cells in space of degenerated axon, injury triggers protein production for reconstruction • Growth cone - neurites (sprouts) try to reach distal portion of axon • AXON CAN REGENERATE if cell body/nucleus are intact

Neuron Structure - Axons

• Single cytoplasmic extension from cell body • Thinner and longer than dendrites • Branches at distal end • Most covered in myelin sheath • A "nerve fiber" is axon plus protective myelin sheath • Efferent (sending out) - Transmits information away from cell body • Segments: Initial segment called hillock + Axon + Terminal Boutons (synaptic boutons)

Microglia

• Small cells with smallest percentage of glia population in CNS • Activate when antigens present in CNS • Travel to site of neuronal insult/injury and phagocytose cellular debris leaving a cavity • Which glial cell fills the cavity left from microglial phagocytosis? - astrocytes

Neuroglia

• Support cells of the nervous system • Small, but 40-50x more numerous than neurons • Found in: Gray & white matter; CNS and PNS • Four types in CNS: Astrocytes; Oligodendroglia; Microglia; Ependymal cells -astrocytes provide structure -microglia are activated in injury -oligodendroglia have myelin sheath -ependymal cells line ventricles • In PNS: Schwann cells (and satellite cells) -Schwann cell is main cell in PNS, clean up after neural injury

Cells of the PNS and CNS

• Two primary types of cells: neurons and neuroglia (glial cells) • *Neurons* communicate with nerve impulses within the nervous system; send excitatory and inhibitory impulses • *Glial cells* support, protect, and repair

Injury to Neurons in CNS

• With injury, inc edema (swelling), inc protein production, changes in cell body/nucleus, some cells survive, others don't • Glial reaction: microglia and astrocytes - phagocytosis and cystic cavity • Some very recent research evidence of possible regenerative ability in parts of CNS with certain txs

Astrocytes

•Fill interneuronal space in CNS - Separate neurons from each other except at synaptic cleft; Provide stiffness and overall support • Contribute to lining of blood-brain barrier • Aid in neural recovery by sealing cavity (following damage/injury) and forming a cyst (in large areas) or filling the space with a glial scar