Transcript Nervous System: General Principles

Nervous System:
General Principles
PA 481 C
Anatomy & Physiology
Tony Serino. Ph.D.
Nervous System
• Controls and/or modifies all other systems
• Rapid response time
• Usually short duration
Functional Areas
Divisions of the Nervous System
Nervous Tissue
• Non-excitable Tissue (Supportive cells)
– Neuroglia –present in CNS
– Schwann and Satellite cells –present in PNS
• Neurons (excitable tissue)
– Initiate and conduct electrical signals (action potentials)
Neuroglia (glial cells)
•Form BBB
•Regulate microenvironment
•Pass on nutrients; get rid of waste
Phagocytic, protective
Neuroglia
•Line cavities
•Create CSF
Secrete myelin in CNS
PNS Supportive Cells
• Schwann cells –secrete myelin in PNS
• Satellite cells –surround neuron cell bodies in PNS
Neuron Anatomy
Axonal terminal
Nerve ending
Synaptic boutons
Synaptic knobs
Functional Zones of a Neuron
Receptor Zone
Initial segment of Axon
(trigger zone)
Nerve
endings
Axon
Myelination
• In PNS, a Schwann cell
wraps and individual
segment of a single axon
• In the CNS, an
oligodendrocyte
performs the same
function but can attach
to more than one axon
Node of Ranvier: gaps in myelin sheath
Types of Neurons
• Anatomical classification
– Based on number of process projecting from
cell body
• Functional Classification
– Based on location of neuron and direction of
information flow
General Terms
• Ganglia vs. Nuclei
– Areas of densely packed nerve cell bodies
– Ganglia are usually found in PNS
– Nuclei are found in CNS
• Nerve vs. nerve fiber
– A nerve is a dissectible structure containing
hundreds of axons
– A nerve fiber is a single axon
• CT sheaths covering peripheral nerves:
Nerve CT sheaths
Synapses
• Areas where neurons communicate with
other cells
• Can be chemical (with neurotransmitters)
or electrical (gap junctions)
Anatomy of Synapse (chemical)
Neurotransmission ends when NT diffuses away,
re-absorbed by presynaptic neuron, or NT metabolized
(degraded) by enzymes in cleft
Neurotransmission
• Electrical signal (action potential (AP)) descends
axon to synaptic knob (nerve end)
• Depolarization opens Ca++ channels to open in
presynaptic membrane
• Triggers a number of synaptic vesicles to fuse
with outer membrane
• Dumps neurotransmitter (NT) into synaptic cleft
• NT diffuses across cleft and binds to receptor on
postsynaptic membrane
• This leads to channels opening on postsynaptic
membrane changing the membrane’s potential
Types of Anatomical Synapses
Membrane Potentials
• Produced by the unequal distribution of ions
across a selectively permeable membrane
• The inside of the cell is called negative by
convention
• The intensity of the ion difference is
expressed as voltage (measured in
millivolts (mV))
Measuring Membrane Potentials
Resting Membrane Potential
Parameters necessary to create a resting membrane potential:
•A semi-permeable membrane
•Distribution of ions across membrane
•Presence of large non-diffusible anions in interior
•Na-K pump (3 Na+ out for every 2 K+ in)
Gated Channel Proteins
• Opening gate allows ions to travel into or
out of the cell thereby changing the
membrane potential
• Can be controlled chemically or electrically
Chemically Gated Channel Protein
Voltage (electrically) Gated
Channel Protein
Graded Potentials
Depolarization
Inside of cell becomes
less negative
•Transient
•Decremental
•Most due to chemically
gated channels opening
•Can be summated
•May be excitatory or
inhibitory
Will only trigger AP if the
threshold of the neuron is
reached.
Hyperpolarization
Inside of cell becomes
more negative
Summation
•Temporal –a single axon fires repeatedly
•Spatial –two or more axons fire simultaneously
Typical Receptor Zone Activity
Action Potentials
• Wave-like, massive depolarization
• Propagated down entire length of
axon or muscle cell membrane
• All or none
• No summation possible
• Due to opening of voltage gated
channels and corresponding positive
feedback cycle established
–
–
–
–
1. Foot –graded potentials
2. Uplimb –fast depolarization
3. Downlimb –fast repolarization
4. After Hyperpolarization –overshoot
due to ion distribution
2
3
1
4
Events in Membrane during the AP
Refractory Periods
Foot
AP Propagation
The depolarization event triggers
depolarization in the next area of the
axon membrane; followed by repolarization. In this
way the AP appears to move in a wave-like fashion
over an unmyelinated axon membrane.
AP propagation
in unmyelinated
axons
The depolarization event triggers
depolarization in the next area of the
axon membrane; followed by repolarization. In
this way the AP appears to move in a wave-like
fashion over an unmyelinated axon membrane.
AP propagation in myelinated axons
The AP appears to jump from node to node (saltatory conduction);
the myelin sheath eliminates the need to depolarize the
entire membrane.
Axonal
Transport
• Anterograde –towards synapse; flow of
synaptic vesicles, mitochondria, etc.
• Retrograde –towards CB; recycled
membrane vesicles, neuromodulators,
etc.
Regeneration of Nerve Fibers
•Damage to nerve tissue is serious because mature
neurons are post-mitotic cells
•If the soma of a damaged nerve remains intact,
damage may be repaired
•Regeneration involves coordinated activity among:
– remove debris
–form regeneration tube and secrete growth factors
–regenerate damaged part
Response to Injury
If contact with tube is not established then no
regeneration and a traumatic neuroma forms
• Anterograde degeneration with
some retrograde; phagocytic cells
(from Schwann cells, microglia or
monocytes) remove fragments of
axon and myelin sheath
• Cell body swells, nucleus moves
peripherally
• Loss of Nissl substance
(chromatolysis)
• In the PNS, some Schwann cells
remain and form a tubular
structure distal to injury; if gap or
scarring is not great axon
regeneration may occur with
growth down tube
• In the CNS, glial scar tissue seems
to prevent regeneration
Regeneration in PNS
Drug Intervention Possibilities
A.
B.
C.
D.
E.
F.
G.
H.
Increase leakage and breakdown
of NT from vesicles
Agonize NT release
Block NT release
Inhibit NT synthesis
Block NT uptake
Block degradative enzymes in
cleft
Bind to post-synaptic receptor
Stimulate or inhibit second
messengers in post-synaptic cell