Neurons and Supporting Cells

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Nervous System

 

 

 

 

 

 

 

Neurons

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Classification of Neurons and Nerves

 

 

 

 

 

 

 

Supporting Cells

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Neurilemma and Myelin Sheath

 

 

 

 

 

Myelin Sheath in PNS

 

 

 

Myelin Sheath in CNS

 

 

 

 

Regeneration of a cut axon

 

 

 

 

 

 

Neurotrophins

 

 

 

 

Functions of Astrocytes

 

 

 

 

 

 

 

 

Blood-Brain Barrier

 

 

 

 

 Electrical Activity in Axons

 

 

 

 

 

 

 

 

Ion Gating in Axons/ Action Potentials

 

 

 

 

 

 

 

 

 

 

 

All or None Law

 

 

 

Stimulus intensity

 

Refractory periods

 

 

 

 

Cable properties of Neurons

 

 

Conduction of Nerve Impulses

Unmyelinated

 

 

Myelinated

 

 

 

The synapse

 

 

 

 

 

 

 

Electrical synapses: Gap Junction

 

 

 

 

 

 

 

 

 

Chemical Synapses

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Acetylcholine

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Monoamines

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Serotonin

 

 

 

 

 

 

 

 

 

Dopamine

 

 

 

Nigrostriatal Dopamine

 

 

 

 

 

 

 

 

Mesolimbic Dopamine

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Norepinephrine

 

 

 

 

Other neurotransmitters

Amino Acids

Excitatory

 

 

 

 

 

 

 

 

Inhibitory

 

 

 

 

 

 

 

Poly peptides

 

 

Synaptic Plasticity

 

 

 

Endogenous Opioids

 

 

 

 

 

 

Neuropeptide Y

 

 

 

 

Endocannabinioids

 

 

 

 

 

 

Nitric Oxide and Carbon Monoxide

 

 

 

 

 

 

 

 

 

 

Long-term potentiation

 

 

 

 

 

 

 

Synaptic Inhibition

 

Central Nervous System (CNS):

·         brain and spinal cord.

Peripheral Nervous System (PNS):

·         cranial nerves and spinal nerves

Cell Types:

  • Neurons and supporting cells (5x)
  • Neuroglial or glial cells can divide by mitosis, neurons cannot. Brain tumors(adult) made of glial cells.

 

Composed of:

·         Dendrite

·         Axon

·         Cell body

Cell body

·         Nucleus

·         Macromolecule production

·         Endoplasmic reticulum called Nissil bodies (chapter3)

·         Clusters of cell bodies called nuclei in CNS

·         Clusters of cell bodies called ganglia in PNS

Dendrite

·         Processes

·         Transmit electrical impulse to cell body

Axon

·         Conducts impulses away from cell body

·         Length 1mm to 1 meter (in whale can be very long)

·         Axon hillock is site of impulse origin

·         Axon collaterals are side branches off axon

·         Axoplasmic flow is cytoplasmic movement from contractions

·         Axonal transport uses microtubules to transport materials

 

Sensory or Afferent: into CNS

Motor or efferent: out of CNS

Somatic: reflex and voluntary control

Autonomic: involuntary muscles, smooth and cardiac, glands

Sympathetic

Parasympathetic

Association  or interneurons in CNS

Cell shapes:

Pseudounipolar- letter T, sensory neuron, acts like axon

Bipolar- 2 processes, retina of eye

Multipolar-1 process, motor neuron

Nerve: bundle of axons outside CNS.

 

 

Derived from ectoderm like neurons.

PNS:

Schwann cells, myelin sheath on axon

Satellite cell or ganglionic gliocytes support neuron cell bodies in ganglia

CNS:

·         Oligodendrocytes, myelin sheath in CNS

·         Microglia, eat invaders and waste

·         Astrocytes, reglulate external environment

·         Ependymal cell, line cavities of brain and spinal cord

Act as neural stem cells!

 

 MS destroys myelin sheath. Caused by autoimmune attack on oligodendrocytes and myelin, triggered by viruses. Genetic component too.

 

 

 

 

In PNS: Sheath of Schwann or neurilemma

·         Both PNS and CNS have myelin sheath

·         Short axons are unmyelinated

·         Myelin increases nerve impulse speed.

 

Formed by Schwann cells, wrapped like electrician tape, cytoplasm squeezed to outside like toothpaste.

Leaves gaps called Nodes of Ranvier

 

  • Formed by oligodendrocytes
  • Occurs postnatally-Developmental importance!
  • Form around many axons
  • White color
  • Grey matter is unmyelinated neurons

 

 

Axon of peripheral nerve cut

  • Schwann cells phagocytose axon form a regeneration tube, axon on cell body grows toward correct destination.
  • Regeneration is limited in CNS due to discontinuous neurilemma, inhibitory molecules, and apoptosis in other neurons.

 

 

Nerve Growth Factor (NGF)

NGF maintains sympathetic ganglia, sensory neuron regeneration

G(lial)DNF:

Maintains spinal motor neuron and dopamine neurons.

 Interact with synapse area and capillaries

Influence neuron/neuron and neuron/blood interactions

Astrocytes may:

  1. Take up K+ from extracellular fluid
  2. Take up neurotransmitters:glutamate
  3. Take up glucose from blood, lactate used as energy source by neuron
  4. Help form synapses in CNS
  5. Induce formation of blood-brain barrier

 

 

Capillaries in brain have tight junctions between cells.  Astrocytes involved.

Some drugs can't cross the blood brain barrier

Dopamine or some antibiotics

Use L-dopa or antibiotics that can cross.

 

Action potential or Nerve impulse

  • Movement of Na+ and K+ ions across neuron plasma membrane
  • All cells have a membrane potential. Measured  in voltage.
  • In neurons the resting potential is -70 mV
  • Na/K pumps, - ions, proteins etc contribute.
  • More Na+out of cell. More K+ in cell
  • Oscilloscope shows when inside becomes positive when line goes up. Called depolarization (excitatory)
  • Line goes down repolarization.
  • Lines goes below resting potential called hyperpolarization. (Inhibitory)

Membrane proteins

  • Gated Channels: Voltage regulated
  • Sodium channels always closed in resting cell
  • Some K channels are open in resting cell and some are closed.
  • During application of + charge to axon,
  • Na gates open, Na goes down concentration gradient into cell. Cell is +.(positive feedback loop)
  • K gates open--K rushes out--Cell becomes negative. (neg feedback loop)
  • Na gates close.

 

Anesthetics reversibly block action potential in sensory neuron by binding voltage-gated Na+ channel.

Examples: cocaine, procaine, lidocaine, tetracaine

 

Once threshold value is achieved action potential occurs to +30 mv.

 

 

Always the same change in voltage. Increased stimulus increases frequency of action potentials. Called recruitment.

 

Time during which action potential can not occur. Due to ball and chain blocking channel or other molecular configuration

Does not take the movement of many ions to generate an action potential.

 

Transmission of properties through the cytoplasm of cell. Very weak in neurons.

 

+ charges conducted by cable properties to adjacent region and starts  next depolarization.

 

Each action potential follows along neuron. Slowed by each channel,  and moves in one direction (refractory period) 1 m/second

 

Much faster, less action potentials needed, channels at nodes of Ranvier, salutatory conduction. 225 mph

Diameter of neuron also influences speed. Thicker is faster.

 

Axons stimulate or inhibit the next neuron (gland or muscle) by releasing neurotransmitters(chemicals) across a synapse.

 

Can be between:

Axon axon

Axon dendrite (most common)

Axon cell body

 

Adjacent cells electrically coupled have gap junctions.

·         Smooth muscle and cardiac muscle

·         Excitation and contraction of muscle masses

·         Gap junctions in brain tissue

·         Gap junctions in glial tissue

·         Gap junctions in embryonic tissue, disappear during specialization

 

 

One way from terminal boutons across synaptic cleft.

 

·         Neurotransmitters in synaptic vesicles fuse with membrane.

·         # of vesicles depends on frequency of action potential.

·         Vesicles at docking sites forming a fusion complex with presynaptic membrane.

·         Ca 2+channels  at  axon terminal near docking sites.

·         AP arrives open Ca channel.

·         Ca 2+ comes in.

·         Triggers fusion.

·         Ca2+ activates calmodulin, which activates protein kinase. Protein kinase adds phosphate to synapsins.

·         Tetanus toxin(inhibit) and botulinum toxin(Ach)  are proteases that destroy parts of fusion complex and inhibit exocytosis.

·         Neurotransmitters bind receptor proteins.

·         Gates in postsynaptic membrane open.

·         Chemically regulated channels.

·         Excitatory postsynaptic potential (EPSP)

·         Inhibitory  postsynaptic potential(IPSP)

 

 

Can cause EPSP or IPSP

CNS and somatic motor neurons

Different Ach receptors

Nicotinic Ach: skeletal muscles

Muscarinic Ach: smooth muscle, cardiac muscle

And glands

 

Ligand-operated channels: Channel in receptor

Nicotinic receptor has 5 subunits. 2 subunits bind Ach, channel opens when both subunits bound by ligand. Na and K both flow causing EPSP.

 

EPSP can sum and exhibit graded response.

 

Myasthenia gravis: Ach receptors blocked by antibodies.

 

Tetrodotoxin blocks Na channels.

 

Muscarinic Ach: one subunit

  • Ligand binds and activates G protein
  • Alpha, Beta, Gamma on receptor bound to GDP
  • GDP leaves
  • Alpha binds GTP and  dissociates
  • Beta gamma or alpha binds channel
  • GTP-GDP causes subunit to go back to receptor and close channel.
  • Binds K Channels.
  • Hyperpolarization or IPSP

Examples of G protein action:

 

  • Heart Muscle-beta gamma binds K channel, open channel, out goes K, IPSP, slows heart.

 

  • Smooth muscle- alpha binds K channel, channel closes, K flow is stopped, depolarization, contraction of stomach

Acetylcholinesterase (AChE) --inactivates Ach

 

Nerve gas inhibits AChE. Dursban

 

In PNS Ach produces "end-plate potentials" at muscle fibers.

 

Curare (South American Indians) competes with Ach for nicotinic receptors and reduces end plate potentials.

 

Produces EPSP and IPSP in autonomic nervous system controlling heart, blood vessels, visceral organs and glands.

 

Ach used in CNS also.

 

Alzheimers associated with loss of cholinergic neurons. (hippocampus and cerebral cortex) Treated with AChE.

 

In CNS Examples:

Tyrosine

Catecholamines

Dopamine,

Norepinephrine: both hormone and neurotransmitter

Epinephrine (adrenaline) hormone from adrenal gland

Tyrptophan

Serotonin-

 

Inhibition of Monoamines after release:

  1. Reuptake into presynaptic membrane
  2. Degradation by monoamine oxidase (MAO)
  3. Postsynaptic degradation by catechol-O-methyltransferase (COMT)

 

MAO inhibitors stop degradation of monoamines and serotonin.  Treatment for Parkinson's (dopamine) and depression.

 

Work via second messenger cAMP

  • Norepinephrine binds receptor
  • Alpha dissociates binds Adenylate cyclase
  • ATP becomes cAMP
  • Protein kinase activated
  • Opens ion channels
  • Phosphorylates proteins

 

5-HT used in raphe nuclei in midline of brain stem.

Regulates mood, behavior, appetite, and cerebral circulation.

LSD mimics 5-HT

SSRI- Serotonin specific reuptake inhibitors include

Prozac, Paxil, Zoloft and Luvox

Many different serotonin receptors.

 

 

Cell bodies of dopaminergic neurons concentrated in midbrain.

Axons involved in Motor control

Axons involved in emotional reward

 

 

Cell bodies in substantial nigra which sends fibers to corpus striatum. Regions part of basal nuclei, deep in cerebrum involved in movement.

Parkinsons disease is caused by degeneration of dopaminergic neurons in substantia nigra.

 

Treat with MAO inhibitors and L-Dopa to increase dopamine transmission.

 

 

Neurons originate in midbrain and send axons to forebrain (limbic system)

 

Involved in behavior

 

Twin studies show D2 subtype of dopamine receptors implicated in alcoholism

 

Cocaine, morphine, amphetamines activate dopaminergic pathways.

 

Cocaine binds reuptake transporters for dopamine, norepinephrine, and serotonin. Overstimulation.

 

 

 

  • Alcohol, amphetamines, cocaine, marijuana, nicotine, and  morphine stimulate dopaminergic neurons in midbrain and end in nucleus accumbens
  • All drugs for schizophrenia are antagonist of D2 subtype of dopamine receptor
  • Overactivity of mesolymbic dopamine pathways contributes to schizophrenia. Other transmitter abnormalities can contribute as well.

 

Used in CNS(behavior arousal) and PNS(cardiac, smooth, glands)

 

Amphetamines stimulate norepinephrine pathways.

 

In CNS

Glutamate

Aspartic acid

 Cause EPSP

Glutamate receptor encloses ion channel

3 types

  1. NMDA
  2. AMPA
  3. Kainite receptor

NMDA receptors involved in memory storage, are complex and permit the entry of Ca and NA into postsynaptic neuron

 

Glycine-IPSP

Used to inhibit muscles of opposing muscle groups.

Strychnine blocks glycine receptors, die due to asphyxiation, diaphragm won't relax

GABA (glutamic acid)-IPSP

Valium (benzodiaxepines) increase GABA to activate receptors. Involved in motor control. Treats anxiety and sleeplessness.

 

CCK (also hormone)-makes you feel full?

Substance P-mediates pain

 

Synapses can change at the molecular level.

Can occur in hours. May have role in learning.

 

 

Made by brain and pituitary gland

B-endorphin

Enkephalins

Dynorphin

Block pain

Naloxone blocks receptors.

 

Inhibits glutamate in hippocampus

Stimulates appetite

Leptin suppresses appetite by inhibiting release of neuropeptide Y.

 

Binds the same as THC receptors

Reverse neurotransmitter

Lipid

Inhibit GABA

 

 

 

 

Relaxes smooth muscle

Kills bacteria

Stimulates cGMP

Involved in erection

Viagra increases action of NO

Knowledge of NO used to treat a variety of conditions.

 

Synaptic potentials can sum. Spatial:  # of presynaptic axons sum on one postsynaptic membrane.

Temporal- # of waves of release.

 

LPT-priming increases potenitation or excitability. Learning.

Mice with enhanced NMDA receptors were smarter

 

Too much glutamate causes cell death.

PCP blocks NMDA receptors.

 

EPSP + IPSP

 

Opiates are analgesic because they block neurons that have substance P.