THE NERVOUS SYSTEM: NEURAL TISSUE

1

• THE NERVOUS SYSTEM NEURAL TISSUE

2
Two organ systems coordinate and direct
activities of body

• Nervous system
• Swift, brief responses to stimuli
• Endocrine system
• Adjusts metabolic operations
• Directs long-term changes

3
An Overview of the Nervous System
4
Divisions of the nervous system
5
Anatomical Classification of the Nervous System

• Central Nervous System
• Brain and spinal cord
• Peripheral Nervous System
• All neural tissue outside CNS

6
Functional divisions of nervous system

• Afferent
• Sensory information from receptors to CNS
• Efferent
• Motor commands to muscles and glands
• Somatic division
• Voluntary control over skeletal muscle
• Autonomic division
• Involuntary regulation of smooth and cardiac
  muscle, glands

7
Histology of Neural Tissue
8
Cells in Nervous Tissue

• Neurons

• Neuroglia

9
Neuroglia (Glia)

• about half the volume of cells in the CNS
• smaller than neurons
• 5 to 50 times more numerous
• do NOT generate electrical impulses
• divide by mitosis
• two types in the PNS
• Schwann cells
• Satellite cells
• Four types in the CNS
• Astrocytes
• Oligodendrocytes
• Microglia
• Ependymal cells

10
Astrocytes

• Largest of glial cells
• Star shaped with many processes
• projecting from the cell body
• Help form and maintain blood-brain barrier
• Provide structural support for neurons
• Maintain the appropriate chemical
• environment for generation of nerve
  impulses/action potentials
• Regulate nutrient concentrations for neuron
  survival
• Regulate ion concentrations - generation of
  action potentials by neurons
• Take up excess neurotransmitters
• Assist in neuronal migration during brain
  development
• Perform repairs to stabilize tissue

11
Oligodendrocytes

• Most common glial cell type
• Each forms myelin sheath around the axons of
  neurons in CNS
• Analogous to Schwann cells of PNS
• Form a supportive network around CNS neurons

• fewer processes than astrocytes
• round or oval cell body

12
Microglia

• few processes
• derived from mesodermal cells
• that also give rise to monocytes
• and macrophages

• Small cells found near blood vessels
• Phagocytic role - clear away dead cells
• protect CNS from disease through phagocytosis of
  microbes
• migrate to areas of injury where they clear away
  debris of
• injured cells - may also kill healthy cells

13
Ependymal Cells

• epithelial cells arranged in a
• single layer
• range in shape from cuboidal
• to columnar

• Form epithelial membrane lining cerebral cavities
  (ventricles) central canal - that contain CSF
• Produce circulate the cerebrospinal fluid (CSF)
  found in these chambers
• CSF colourless liquid that protects the brain
  and SC against
• chemical physical injuries, carries
  oxygen, glucose and other necessary
• chemicals from the blood to neurons and
  neuroglia

14
PNS Satellite Cells

• Flat cells surrounding PNS cell bodies
• Support neurons in the PNS

15
PNS Schwann Cells
Neurilemma

• each cell surrounds multiple unmyelinated PNS
  axons with a single layer of its plasma membrane
• Each cell produces part of the myelin sheath
  surrounding an axon in the PNS
• contributes regeneration of PNS axons

16
Representative Neuron
-neurofilaments or neurofibrils give cell shape
and support - bundles of intermediate
filaments -microtubules move material inside
cell -lipofuscin pigment clumps (harmless aging)
- yellowish brown
1. cell body or soma -single nucleus with
prominent nucleolus -Nissl bodies -rough ER
free ribosomes for protein synthesis -proteins
then replace neuronal cellular components for
growth and repair of damaged axons in the PNS
17
Neurons
2. Cell processes dendrites (little trees) -
the receiving or input portion of the
neuron -short, tapering and highly
branched -surfaces specialized for contact with
other neurons -cytoplasm contains Nissl bodies
mitochondria
18

• 3. Cell processes axons
• Conduct impulses away from cell body-propagates
  nerve impulses to another neuron
• Long, thin cylindrical process of cell
• contains mitochondria, microtubules
  neurofibrils - NO ER/NO protein synth.
• joins the soma at a cone-shaped elevation axon
  hillock
• first part of the axon initial segment
• most impulses arise at the junction of the axon
  hillock and initial segment trigger zone
• cytoplasm axoplasm
• plasma membrane axolemma
• Side branches collaterals arise from the axon
• axon and collaterals end in fine processes called
  axon terminals
• Swollen tips called synaptic end bulbs contain
  vesicles filled with neurotransmitters

19
Structural Classification of Neurons

• Based on number of processes found on cell body
• multipolar several dendrites one axon
• most common cell type in the brain and SC
• bipolar neurons one main dendrite one axon
• found in retina, inner ear olfactory
• unipolar neurons one process only, sensory only
  (touch, stretch)
• develops from a bipolar neuron in the embryo -
  axon and dendrite fuse and then branch into 2
  branches near the soma - both have the structure
  of axons (propagate APs) - the axon that projects
  toward the periphery dendrites

20
Structural Classification of Neurons

• Named for histologist that first described them
  or their appearance

• Purkinje cerebellum
• Renshaw spinal cord

• others are named for shapes
• e.g. pyramidal cells

21
Functional Classification of Neurons

• Sensory (afferent) neurons
• transport sensory information from skin, muscles,
  joints, sense organs viscera to CNS
• Motor (efferent) neurons
• send motor nerve impulses to muscles glands
• Interneurons (association) neurons
• connect sensory to motor neurons
• 90 of neurons in the body

22
The Nerve Impulse
23
Terms to know

• membrane potential electrical voltage
  difference measured across the membrane of a cell
• resting membrane potential membrane potential
  of a neuron measured when it is unstimulated
• results from the build-up of negative ions in the
  cytosol along the inside of the neurons PM
• the outside of the PM becomes more positive
• this difference in charge can be measured as
  potential energy measured in millivolts
• polarization
• depolarization
• repolarization
• hyperpolarization

24
The electric potential across an axonal membrane
can be measured

• the differences in positive and
• negative charges in and out
• of the neuron can be measured by
• electrodes resting membrane potential
• -ranges from -40 to -90 mV

25
Ion Channels

• ion channels in the PM of neurons and muscles
  contributes to their excitability
• when open - ions move down their concentration
  gradients
• channels possess gates to open and close them
• two types gated and non-gated

1. Leakage (non-gated) or Resting channels are
always open, contribute to the resting
potential -nerve cells have more K than Na
leakage channels -as a result, membrane
permeability to K is higher -K leaks out of
cell - inside becomes more negative -K is then
pumped back in
2. Gated channels open and close in response to
a stimulus A. voltage-gated open in response to
change in voltage - participate in the AP B.
ligand-gated open close in response to
particular chemical stimuli (hormone,
neurotransmitter, ion) C. mechanically-gated
open with mechanical stimulation
26
Action Potential

• Resting membrane potential is -70mV
• triggered when the membrane potential reaches a
  threshold usually -55 MV
• if the graded potential change exceeds that of
  threshold Action Potential
• Depolarization is the change from -70mV to 30 mV
• Repolarization is the reversal from 30 mV back
  to -70 mV)

• action potential nerve impulse
• takes place in two stages depolarizing phase
  (more positive) and repolarizing phase (more
  negative - back toward resting potential)
• followed by a hyperpolarizing phase or refractory
  period in which no new AP
• can be generated

http//www.blackwellpublishing.com/matthews/channe
l.html
27
The action potential

• 1. neuron is at resting membrane potential
  (resting MP)
• 2. neuron receives a signal
• Neurotransmitter (NT)
• 3. NT binds ligand-gated sodium channel
• 4. LGNa channel opens
• 5. Na flows into neuron depolarization
• Inside of neuron (i.e. MP) becomes more positive
• 6. if neuron depolarizes enough to Threshold
  Action Potential (AP)
• 7. 1st stage of AP opening of voltage-gated Na
  channels
• 8. even more Na flows in through VGNa channels
  BIG depolarization
• Membrane potential goes from negative to positive
• 9. closing of VGNa channels opening of
  voltage-gated K channels
• 10. BIG outflow of potassium through VGK channels
  repolarization
• Inside of neuron (MP) becomes more negative
• 11. neuron repolarizes so much it goes past
  resting and hyperpolarizes
• 12. closing of VGK channels
• 13. all voltage-gated channels closed, Na/K pump
  resets ion distribution to resting situation

28
Continuous versus Saltatory Conduction

• Continuous conduction (unmyelinated fibers)
• An action potential spreads (propagates) over the
  surface of the axolemma
• as Na flows into the cell during depolarization,
  the voltage of adjacent areas is effected and
  their voltage-gated Na channels open
• step-by-step depolarization of each portion of
  the length of the axolemma

http//highered.mcgraw-hill.com/sites/0072437316/s
tudent_view0/chapter45/animations.html
29
Saltatory Conduction

• Saltatory conduction (myelinated fibers)
• -depolarization only at nodes of Ranvier - areas
  along the axon that are unmyelinated and where
  there is a high density of voltage-gated ion
  channels
• -current carried by ions flowing through
  extracellular fluid from node to node

http//www.blackwellpublishing.com/matthews/action
p.html
30
Rate of Impulse Conduction

• Properties of axon
• Presence or absence of myelin sheath
• Diameter of axon

31
Synaptic Communication
32
Synapses

• Synapse Site of intercellular communication
  between 2 neurons or between a neuron and an
  effector (e.g. muscle neuromuscular junction)
• Permits communication between neurons and other
  cells
• Initiating neuron presynaptic neuron
• Receiving neuron postsynaptic neuron
• You can classify a synapse according to
• 1. the action they produce on the post-synaptic
  neuron excitatory or inhibitory
• 2. the mode of communication chemical vs.
  electrical

33
Synapses Excitatory vs. Inhibitory

• If the NT depolarizes the postsynaptic neuron
  excitatory
• The depolarization event is often called an
  excitatory postsynaptic potential (EPSP)
• Opening of sodium channels or other cation
  channels (inward)
• Some NTs will cause hyperpolarization
  inhibitory
• The hyperpolarization event is often called an
  inhibitory postsynaptic potential (IPSP)
• Opening of chloride channels (inward) or
  potassium channels (outward)
• Neural activity depends on summation of all
  synaptic activity
• Excitatory and inhibitory

34
Synapses

• Electrical
• Direct physical contact between cells required
• Conducted through gap junctions
• Two advantages over chemical synapses
• 1. faster communication almost instantaneous
• 2. synchronization between neurons or muscle
  fibers
• e.g. heart beat

35
Chemical Synapse

• Synapse
• Most are axodendritic axon -gt dendrite
• Some are axoaxonic axon gt axon

http//www.lifesci.ucsb.edu/mcdougal/neurobehavio
r/modules_homework/lect3.dcr
36
Synapses Chemical vs. Electrical

• Chemical
• Membranes of pre and postsynaptic neurons do not
  touch
• Synaptic cleft exists between the 2 neurons 20
  to 50 nm
• the electrical impulse cannot travel across the
  cleft indirect method is required chemical
  messengers (neurotransmitters)
• Most common type of synapse
• The neurotransmitter induces a postsynaptic
  potential in the PS neuron if the potential is
  an EPSP excitatory and an AP results (e.g.
  glutamate)
• If the potential is an IPSP inhibitory and NO
  AP results (e.g. glycine or GABA)
• Communication in one direction only

http//www.blackwellpublishing.com/matthews/nmj.ht
ml
37
The Events in Muscle Contraction

• AP generated at trigger zone in
• pre-synaptic neuron
• 2. AP arrives in end bulb causes entry
• of calcium into end-bulb release
• of Ach
• Binding of Ach to ligand-gated Na
• channels on muscle PM (Ach receptors)
• Na enters muscle cell depolarization
• Muscle membrane potential reaches
• threshold Action Potential
• 6. AP travels through PM of muscle cell into
• T-tubules
• 7. AP passes by sarcoplasmic reticulum
• release of calcium into muscle cell
• 8. Ca binds troponin-tropomyosin complex
• shifts it off myosin binding site
• 9. Cross-bridging between actin and myosin,
• pivoting of myosin head Contraction
• (ATP dependent)

38
The Neuromuscular Junction

• end of neuron (synaptic terminal or axon bulb)
  is in very close association
• with the muscle fiber
• distance between the bulb and the folded
  sarcolemma synaptic cleft
• nerve impulse leads to release of
  neurotransmitter (acetylcholine)
• N.T. binds to receptors on myofibril surface
• binding leads to influx of sodium, potassium
  ions (via channels)
• eventual release of calcium by sarcoplasmic
  recticulum contraction

• Acetylcholinesterase breaks down ACh
• Limits duration of contraction

39
Motor Units

• Each skeletal fiber has only ONE NMJ
• MU Somatic neuron all the skeletal muscle
  fibers it innervates
• Number and size indicate precision of muscle
  control
• Muscle twitch
• Single momentary contraction
• Response to a single stimulus
• All-or-none theory
• Either contracts completely or not at all

• Motor units in a whole muscle fire
  asynchronously
• some fibers are active others are relaxed
• delays muscle fatigue so contraction can be
  sustained

• Muscle fibers of different motor units are
  intermingled so that net distribution of force
  applied to the tendon remains constant even when
  individual muscle groups cycle between
  contraction and relaxation.

40
Motor Tone

• Resting muscle contracts random motor units
• Constant tension created on tendon
• Resting tension muscle tone
• Stabilizes bones and joints

41
Neurotransmitters

• More than 100 identified
• Some bind receptors and cause channels to open
• Others bind receptors and result in a second
  messenger system
• Results in either excitation or inhibition of the
  target

1. small molecules Acetylcholine (ACh) -All
neuromuscular junctions use ACh -ACh also
released at chemical synapses in the PNS and by
some CNS neurons -Can be excitatory at some
synapses and inhibitory at others -Inactivated by
an enzyme acetylcholinesterase
42
Neurotransmitters

• 2. Amino acids glutamate aspartate GABA
• Powerful excitatory effects
• Glutamate is the main excitatory neurotransmitter
  in the CNS
• Stimulate most excitatory neurons in the CNS
  (about ½ the neurons in the brain)
• Binding of glutamate to receptors opens calcium
  channels EPSP
• GABA (gamma amino-butyric acid) is an inhibitory
  neurotransmitter for 1/3 of all brain synapses
• MSG monosodium glutamate
• flavor enhancer since 1900s
• used as a purified salt of L-glutamic acid or in
  a mixture of amino acids
• intermediate in amino acid metabolism, energy
  source for cardiac myocytes
• can cause Chinese Restaurant syndrome numbness,
  muscle weakness and heart palpitations similar
  to effects seen upon Ach administration
• MSG can be converted into ACh via the Citric acid
  cycle
• ACh in the CNS is involved in memory, arousal and
  reward excitatory NT

43
Neurotransmitters

• 3. Biogenic amines modified amino acids
• catecholamines norepinephrine (NE), epinephrine,
  dopamine (tyrosine)
• serotonin - concentrated in neurons found in the
  brain region raphe nucleus
• derived from tryptophan
• sensory perception, temperature regulation, mood
  control, appetite, sleep induction
• feeling of well being
• NE - role in arousal, awakening, deep sleep,
  regulating mood
• epinephrine (adrenaline) - flight or fight
  response
• dopamine - emotional responses and pleasure,
  decreases skeletal muscle tone

44
Removal of Neurotransmitter

• Enzymatic degradation
• acetylcholinesterase
• Uptake by neurons or glia cells
• neurotransmitter transporters
• NE, dopamine, serotonin

45
GABA

• GABA action is affected by a broad range of drugs
  called benzodiazepines
• e.g. lorazepan Ativan
• e.g. diazepam - Valium
• Various uses hynoptic, sedative, anxiolytic,
  anticonvulsant, muscle relaxant, amnesic
• Short lasting half life is less than 12 hours
• hypnotic effects
• insomnia
• Long lasting half life is more than 24 hours
• anxiolytic effects (anti-anxiety drug)
• Acts to enhance GABA
• GABA major inhibitory NT in the CNS
• GABA binds to GABA receptors several types
• Benzodiazepines bind and modulate the activity of
  the GABAA receptor which is the most prolific NT
  receptor in the brain
• GABAA receptor is comprised of 5 protein subunits
• One subunit is the alpha subunit
• BZs bind to the alpha subunit only and increase
  its affinity for binding the GABA
  neurotransmitter
• The GABAA receptor is a ligand-gated chloride
  channel
• Binding of GABA increases the inward flow of
  chloride ions which hyperpolarizes the neuron and
  inhibits its ability to make a new action
  potential
• Therefore BZs potentiate the inhibitory effects
  of GABA

46
Valium

• top selling drug from 1969-1982
• GABA agonist
• Also decreases the synthesis of neurosteroid
  hormones (e.g. DHEA, progesterone) which may
  regulate emotional state
• Acts on areas of the limbic system, the thalamus
  and the hypothalamus (anti-anxiety drug)
• Metabolized by the liver into many metabolites
• Gives rise to a biphasic half live of 1-2 days
  and 2-5 days!
• Lipid-soluble and crosses the blood-brain barrier
  very easily
• Stored in the heart, the muscle and the fat
• Some drugs (barbituates), anti-depressants and
  alchohol can enhance its effect
• Smoking can increase the elimination of valium
  and decrease its effects

47
Dopamine

• Involved in feelings of pleasure, strength
• Also mediates skeletal muscle contraction
• Neurotransmitters like dopamine, serotonin,
  glutamate, acetylcholine etc are secreted and
  then rapidly internalized by transporters in
  order to control their levels within the nervous
  system
• Many drugs affect these transporters
• Ritalin methylphenidate
• 1954 initially prescribed in adults for
  depression and narcolepsy - stimulant
• 1960 prescribed to children with ADD, ADHD -
  depressant
• Reason?? Might be due to an imbalance in dopamine
• Binds both dopamine and norepinephine
  transporters and inhibits their ability to take
  these NTs back up (keeps their levels high in the
  synapse)
• Dopamine transporters (DAT) found in the PM of
  neurons (presynaptic)
• Transports dopamine back into the neuron along
  with sodium ions (symporter)
• This terminates the dopamine signal
• Chloride ions are also required to enter the
  neuron to prevent depolarization
• In adults these transporters regulate dopamine
  levels
• Cocaine binds and inhibits DATs increasing
  dopamine in the synapse
• Amphetamines binds amphetamine receptors on a
  neuron which causes the internalization of the
  DAT into the neuron increasing dopamine in the
  synapse

48
Neuropeptides

• widespread in both CNS and PNS
• excitatory and inhibitory
• act as hormones elsewhere in the body
• -Substance P -- enhances our perception of pain
• -opioid peptides endorphins - released during
  stress, exercise
• -breaks down bradykinins (pain chemicals),
  boosts
• the immune system and slows the growth of
  cancer
• cells
• -binds to mu-opioid receptors
• -released by the neurons of the Hypothalamus
  and by
• the cells of the pituitary
• enkephalins - analgesics
• -breaks down bradykinins (200x stronger than
  morphine)
• -pain-relieving effect by blocking the
  release of
• substance P
• dynorphins - regulates pain and emotions

acupuncture may produce loss of pain sensation
because of release of opioid-like substances such
as endorphins or dynorphins
49
Morphine

• Opiate analgesic
• Principal agent in opium
• Acts on the CNS
• Acts on the GI tract decrease motility,
  decrease gastric secretion, decreases gastric
  empyting, increases fluid absorption
• Other opiates heroin, codeine, thebaine
• Acts on the neurons of the CNS (specifically the
  nucleus accumbens of the basal ganglia)
• Binds to the mu-opioid receptor
• Found throughout the brain especially in the
  posterior amygdala, the hypothalamus and thalams,
  the basal ganglia, the dorsal horn of the spinal
  cord and the trigeminal nerve
• Relieves the inhibition of GABA release by
  presynaptic neurons
• Also relieves the inhibition of dopamine release
  (addiction)
• Binding activates the receptor and gives rise to
  analgesia, euporia, sedation, dependence and
  respiratory and BP depression.
• Acts on the immune system! increase incidence
  of addiction in those that suffer from pneumonia,
  TB and HIV
• Activates a type of immune cell called a
  dendritic cell decrease their activation of B
  cells decreased antibody production decrease
  immune function