Neuronssynapses 100408015114-phpapp01

Nervous System


2 types of cells in the nervous system:





Neurons.
Supporting cells.

Nervous system is divided into:


Central nervous system (CNS):





Brain.
Spinal cord.

Peripheral nervous system (PNS):



Cranial nerves.
Spinal nerves.

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Neurons


Basic structural and functional units of the
nervous system.







Cannot divide by mitosis.

Respond to physical and chemical stimuli.
Produce and conduct electrochemical impulses.
Release chemical regulators.
Nerve:


Bundle of axons located outside CNS.


Most composed of both motor and sensory fibers.
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Neurons


Cell body (perikaryon):





“Nutrition center.”
Cell bodies within CNS clustered into nuclei, and in PNS in
ganglia.

Dendrites:





(continued)

Provide receptive area.
Transmit electrical impulses to cell body.

Axon:
 Conducts impulses away from cell body.


Axoplasmic flow:




Proteins and other molecules are transported by rhythmic contractions
to nerve endings.

Axonal transport:



Employs microtubules for transport.
May occur in orthograde www.freelivedoctor
or retrograde direction.

Neurons

(continued)

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Functional Classification of
Neurons




Based upon direction
impulses conducted.
Sensory or afferent:




Motor or efferent:




Conduct impulses from
sensory receptors into
CNS.
Conduct impulses out of
CNS to effector organs.

Association or
interneurons:




Located entirely within
the CNS.
Serve an integrative
function.

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Structural Classification of
Neurons


Based on the # of
processes that extend
from cell body.


Pseudounipolar:


Short single process
that branches like a T.




Bipolar neurons:


Have 2 processes.




Sensory neurons.

Retina of the eye.

Multipolar:


Have several dendrites
and 1 axon.


Motor neuron.

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PNS Supporting Cells


Schwaan cells:







Nodes of Ranvier:




Successive wrapping of the cell membrane.
Outer surface encased in glycoprotein basement
membrane.
Provide insulation.
Unmyelinated areas between adjacent Schwaan
cells that produce nerve impulses.

Satellite cells:


Support neuron cell bodies within ganglia.
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CNS Supporting Cells


Oligodendrocytes:



Process occurs mostly postnatally.
Each has extensions that form myelin sheaths around
several axons.


Insulation.

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Nerve Regeneration


Schwann cells:




Act as phagocytes, as the distal neuronal
portion degenerates.
Surrounded by basement membrane, form
regeneration tube:





Serve as guide for axon.
Send out chemicals that attract the growing
axon.
Axon tip connected to cell body begins to grow
towards destination.
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Nerve Regeneration



CNS has limited
ability to regenerate:




Absence of
continuous basement
membrane.
Oligodendrocytes
molecules inhibit
neuronal growth.

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(continued)

Neurotrophins



Promote neuron growth.
Nerve growth factors include:




Nerve growth factor (NGF), brain-derived
neurotrophic factor (BDNF), glial-derived
neurotrophic factor (GDNF), neurotrophin-3,
and neurotrophin-4/5.

Fetus:


Embryonic development of sensory neurons
and sympathetic ganglia (NGF and
neurotrophin-3).
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Neurotrophins


Adult:










(continued)

Maintenance of sympathetic ganglia
(NGF).
Mature sensory neurons need for
regeneration.
Required to maintain spinal neurons
(GDNF).
Sustain neurons that use dopamine
(GDNF).

Myelin-associated inhibitory proteins:


Inhibit axon regeneration.
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

Astrocytes:









Most abundant glial cell.
Vascular processes
terminate in end-feet that
surround the capillaries.
Stimulate tight junctions,
contributing to blood-brain
barrier.
Regulate external
environment of K+ and pH.
Take up K+ from ECF, NTs
released from axons, and
lactic acid (convert for ATP
production).


Other extensions adjacent
to synapses.

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(continued)



Microglia:




(continued)

Phagocytes, migratory.

Ependymal cells:





Secrete CSF.
Line ventricles.
Function as neural stem cells.
Can divide and progeny differentiate.
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Blood-Brain Barrier


Capillaries in brain do not have pores
between adjacent endothelial cells.




Joined by tight junctions.

Molecules within brain capillaries moved
selectively through endothelial cells by:





Diffusion.
Active transport.
Endocytosis.
Exocytosis.
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Electrical Activity of Axons


All cells maintain a resting membrane potential
(RMP):


Potential voltage difference across membrane.






Permeability of cell membrane:





Largely the result of negatively charged organic molecules
within the cell.
Limited diffusion of positively charged inorganic ions.
Electrochemical gradients of Na+ and K+.
Na+/K+ ATPase pump.

Excitability/irritability:


Ability to produce and conduct electrical impulses.
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Electrical Activity of Axons




Increase in membrane permeability
for specific ion can be measured by
placing 2 electrodes (1 inside and 1
outside the cell).
Depolarization:




Repolarization:




Potential difference reduced
(become more positive).
Return to resting membrane
potential (become more negative).

Hyperpolarization:


More negative than RMP.

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(continued)

Ion Gating in Axons




Changes in membrane potential caused by ion flow through
ion channels.
Voltage gated (VG) channels open in response to change in
membrane potential.


Gated channels are part of proteins that comprise the channel.




2 types of channels for K+:





Can be open or closed in response to change.
1 always open.
1 closed in resting cell.

Channel for Na+:


Always closed in resting cells.


Some Na+ does leak into the cells.
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Ion Gating in Axons

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(continued)

Action Potentials (APs)



Stimulus causes depolarization to threshold.
VG Na+ channels open.


Electrochemical gradient inward.








+ feedback loop.

Rapid reversal in membrane potential from –70 to +
30 mV.
VG Na+ channels become inactivated.

VG K+ channels open.




Electrochemical gradient outward.
- feedback loop.
Restore original RMP.
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(continued)

Membrane Permeabilites




AP is produced
by an increase in
Na+ permeability.
After short delay,
increase in K+
permeability.

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

Depolarization and repolarization occur via diffusion, do
not require active transport.








When threshold reached, maximum potential change occurs.
Amplitude does not normally become more positive than + 30
mV because VG Na+ channels close quickly and VG K+
channels open.
Duration is the same, only open for a fixed period of time.

Coding for Stimulus Intensity:




Once AP completed, Na+/K+ ATPase pump extrudes Na+, and
recovers K+.

All or none:




(continued)

Increased frequency of AP indicates greater stimulus strength.

Recruitment:


Stronger stimuli can activate more axons with a higher
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threshold.

Refractory Periods


Absolute refractory
period:




Axon membrane is
incapable of producing
another AP.

Relative refractory
period:






VG ion channel shape
alters at the molecular
level.
VG K+ channels are
open.
Axon membrane can
produce another action
potential, but requires
stronger stimulus.

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Cable Properties of Neurons




Ability of neuron to transmit charge through
cytoplasm.
Axon cable properties are poor:






High internal resistance.
Many charges leak out of the axon through
membrane.

An AP does not travel down the entire axon.
Each AP is a stimulus to produce another AP
in the next region of membrane with VG
channels.
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Conduction in an Unmyelinated
Axon




Cable spread of
depolarization with
influx of Na+ depolarizes
the adjacent region
membrane, propagating
the AP.
Conduction rate is slow.




AP must be produced at
every fraction of
micrometer.

Occurs in 1 direction;
previous region is in its
refractory period.

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Conduction in Myelinated Axon








Myelin prevents movement
of Na+ and K+ through the
membrane.
Interruption in myelin
(Nodes of Ranvier) contain
VG Na+ and K+ channels.
AP occurs only at the
nodes.
 AP at 1 node
depolarizes membrane
to reach threshold at
next node.
Saltatory conduction
(leaps).
 Fast rate of conduction.
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Synapse









Functional connection between a neuron and
another neuron or effector cell.
Transmission in one direction only.
Axon of first (presynaptic) to second
(postsynaptic) neuron.
Synaptic transmission is through a chemical
gated channel.
Presynaptic terminal (bouton) releases a
neurotransmitter (NT).
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Electrical Synapse




Impulses can be
regenerated without
interruption in adjacent
cells.
Gap junctions:






Adjacent cells electrically
coupled through a
channel.
Each gap junction is
composed of 12
connexin proteins.

Examples:


Smooth and cardiac
muscles, brain, and glial
cells.

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Chemical Synapse








Terminal bouton is
separated from
postsynaptic cell by
synaptic cleft.
NTs are released from
synaptic vesicles.
Vesicles fuse with axon
membrane and NT
released by exocytosis.
Amount of NTs
released depends upon
frequency of AP.

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Synaptic Transmission





NT release is rapid because many vesicles
form fusion-complexes at “docking site.”
AP travels down axon to bouton.
VG Ca2+ channels open.







Ca2+ enters bouton down concentration gradient.
Inward diffusion triggers rapid fusion of synaptic
vesicles and release of NTs.

Ca2+ activates calmodulin, which activates
protein kinase.
Protein kinase phosphorylates synapsins.


Synapsins aid in the fusion of synaptic vesicles.
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Synaptic Transmission






NTs are released and diffuse across synaptic
cleft.
NT (ligand) binds to specific receptor proteins
in postsynaptic cell membrane.
Chemically-regulated gated ion channels
open.





(continued)

EPSP: depolarization.
IPSP: hyperpolarization.

Neurotransmitter inactivated to end
transmission.
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Chemical Synapses


EPSP (excitatory
postsynaptic
potential):




Depolarization.

IPSP (inhibitory
postsynaptic
potential):


Hyperpolarizatio
n
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Acetylcholine (ACh) as NT


ACh is both an excitatory and inhibitory NT,
depending on organ involved.




Nicotinic ACh receptors:




Causes the opening of chemical gated ion
channels.

Found in autonomic ganglia and skeletal muscle
fibers.

Muscarinic ACh receptors:


Found in the plasma membrane of smooth and
cardiac muscle cells, and in cells of particular
glands.
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Ligand-Operated ACh Channels



Most direct mechanism.
Ion channel runs through
receptor.
 Receptor has 5 polypeptide





Channel opens when both sites
bind to ACh.




subunits that enclose ion
channel.
2 subunits contain ACh binding
sites.

Permits diffusion of Na+ into
and K+ out of postsynaptic cell.

Inward flow of Na+ dominates.


Produces EPSPs.
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G Protein-Operated ACh
Channel









Only 1 subunit.
Ion channels are
separate proteins
located away from the
receptors.
Binding of ACh
activates alpha Gprotein subunit.
Alpha subunit
dissociates.
Alpha subunit or the
beta-gamma complex
diffuses through
membrane until it binds
to ion channel, opening
it.

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Acetylcholinesterase (AChE)


Enzyme that inactivates ACh.




Present on postsynaptic membrane or immediately outside the
membrane.

Prevents continued stimulation.

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ACh in CNS


Cholinergic neurons:








Use ACh as NT.
Axon bouton synapses with dendrites or cell body
of another neuron.

First VG channels are located at axon hillock.
EPSPs spread by cable properties to initial
segment of axon.
Gradations in strength of EPSPs above
threshold determine frequency of APs
produced at axon hillock.
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ACh in PNS


Somatic motor neurons synapse with
skeletal muscle fibers.





Release ACh from boutons.
Produces end-plate potential (EPSPs).

Depolarization opens VG channels
adjacent to end plate.

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Monoamines as NT


Monoamine NTs:










Epinephrine.
Norepinephrine.
Serotonin.
Dopamine.

Released by exocytosis from
presynaptic vesicles.
Diffuse across the synaptic cleft.
Interact with specific receptors in
postsynaptic membrane.
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Inhibition of Monoamines
as NT


Reuptake of
monoamines into
presynaptic
membrane.




Enzymatic degradation
of monoamines in
presynaptic membrane
by MAO.

Enzymatic
degradation of
catecholamines in
postsynaptic
membrane by COMT.

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Mechanism of Action












Monoamine NT do not
directly open ion channels.
Act through second
messenger, such as
cAMP.
Binding of norepinephrine
stimulates dissociation of
G-protein alpha subunit.
Alpha subunit binds to
adenylate cyclase,
converting ATP to cAMP.
cAMP activates protein
kinase, phosphorylating
other proteins.
Open ion channels.

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Serotonin as NT






NT (derived from L-tryptophan) for neurons
with cell bodies in raphe nuclei.
Regulation of mood, behavior, appetite, and
cerebral circulation.
SSRIs (serotonin-specific reuptake inhibitors):




Inhibit reuptake and destruction of serotonin,
prolonging the action of NT.
Used as an antidepressant.


Reduces appetite, treatment for anxiety, treatment for
migraine headaches.
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Dopamine an NT



NT for neurons with cell bodies in midbrain.
Axons project into:


Nigrostriatal dopamine system:







Nuerons in substantia nigra send fibers to corpus
straitum.
Initiation of skeletal muscle movement.
Parkinson’s disease: degeneration of neurons in
substantia nigra.

Mesolimbic dopamine system:





Neurons originate in midbrain, send axons to limbic
system.
Involved in behavior and reward.
Addictive drugs:


Promote activity in nucleus accumbens.
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Norepinephrine (NE) as NT



NT in both PNS and CNS.
PNS:


Smooth muscles, cardiac muscle and
glands.




Increase in blood pressure, constriction of
arteries.

CNS:


General behavior.
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Amino Acids as NT






Glutamic acid and aspartic acid:
 Major excitatory NTs in CNS.
Glutamic acid:
 NMDA receptor involved in memory storage.
Glycine:
 Inhibitory, produces IPSPs.
 Opening of Cl- channels in postsynaptic membrane.


Hyperpolarization.

Helps control skeletal movements.
GABA (gamma-aminobutyric acid):
 Most prevalent NT in brain.
 Inhibitory, produces IPSPs.






Hyperpolarizes postsynaptic membrane.


Motor functions in cerebellum.

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Polypeptides as NT


CCK:




Substance P:




Promote satiety following meals.
Major NT in sensations of pain.

Synaptic plasticity (neuromodulating
effects):


Neurons can release classical NT or the
polypeptide NT.
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Polypeptides as NT


Endogenous opiods:


Brain produces its own analgesic endogenous morphine-like
compounds, blocking the release of substance P.

Beta-endorphin, enkephalins, dynorphin.
Neuropeptide Y:
 Most abundant neuropeptide in brain.
 Inhibits glutamate in hippocampus.
 Powerful stimulator of appetite.
NO:












Exerts its effects by stimulation of cGMP.

Macrophages release NO to helps kill bacteria.
Involved in memory and learning.
Smooth muscle relaxation.
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Endogenous Cannabinoids,
Carbon Monoxide


Endocannabinoids:






Bind to the same receptor as THC.
Act as analgesics.
Function as retrograde NT.

Carbon monoxide:





Stimulate production of cGMP within neurons.
Promotes odor adaptation in olfactory
neurons.
May be involved in neuroendocrine regulation
in hypothalamus.
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EPSP



No threshold.
Decreases resting
membrane
potential.








Closer to
threshold.

Graded in
magnitude.
Have no refractory
period.
Can summate.
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Synaptic Integration


EPSPs can
summate, producing
AP.


Spatial summation:




Numerous boutons
converge on a single
postsynaptic neuron
(distance).

Temporal summation:


Successive waves of
neurotransmitter
release (time).
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Long-Term Potentiation




May favor transmission along frequently used
neural pathways.
Neuron is stimulated at high frequency,
enhancing excitability of synapse.




Improves efficacy of synaptic transmission.

Neural pathways in hippocampus use
glutamate, which activates NMDA receptors.


Involved in memory and learning.

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Synaptic Inhibition


Presynaptic inhibition:





Amount of excitatory NT
released is decreased by
effects of second neuron,
whose axon makes
synapses with first neuron’s
axon.

Postsynaptic inhibition
(IPSPs):








No threshold.
Hyperpolarize postsynaptic
membrane.
Increase membrane
potential.
Can summate.
No refractory period.

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