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BIOSC 48
Chapter 7
The Nervous System
BIOSC 48
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Nervous System
Divisions of the Nervous
System:
• Central Nervous System
(CNS)
• Brain
• Spinal cord
• Peripheral Nervous System
(PNS)
• Cranial nerves
• Spinal nerves
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Nervous System
Types of Cells:
• Neurons
• Receive and transmit
information
• Glial cells (neuroglia)
• Support cells
• Physical support and
insulation
• Supply nutrients and gases
• Remove dead cells (clean-up)
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Neurons
Structural and functional units of the nervous system
• Most neurons can’t divide, but can repair
Functions:
• Responds to chemical and physical stimuli
• Conducts electrochemical impulses
• Releases chemical regulators
• Enables perception of sensory stimuli, learning,
memory, and control of muscle and glands
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Neurons
General structure:
Cell body
• Organelles
• Nucleus
• Nissl bodies
(specialized rough
ER)
• Cell body clusters:
• CNS: nuclei
• PNS: ganglia
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Neurons
General structure:
Processes outside the
body
• Dendrites
• Receive impulses
and conducts a
graded impulse
towards the cell
body
• Axon
• Conducts action
potentials away
from the cell body
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Neurons
Axons
• Vary in length (few
mm-m)
• Regions of an axon
• Axon hillock
• Where action
potentials are
generated
• Initial segment
• Axon collateral
• Axon terminal
• Contains vesicles
with
neurotransmitters
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Functional Classification of Neurons
Based on direction and types of impulses
• Sensory neurons
• Conducts impulses:
sensory receptors à
the CNS (afferent)
• Motor neurons
• Conducts impulses:
CNS à target organs
(muscle or glands;
efferent)
• Association/
Interneurons
• Located within CNS
• Integrates functions
of the NS
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Functional Classification of Neurons
Motor Neurons
• Somatic motor neurons
• Reflexes and voluntary control of skeletal muscles
• Autonomic motor neurons
• Involuntary targets (Ex: smooth muscle, cardiac muscle,
and glands
• Subdivisions of the autonomic NS
• Sympathetic “flight or flight”: emergency situations
• Parasympathetic “rest and digest”: normal functions
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Functional Classification of Neurons
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Structural Classification of Neurons
Based on the number of processes that extend from
the cell body
• Pseudounipolar
• Single short process that
branches to form two longer
processes
• Ex: sensory neurons
• Bipolar
• Two processes, one on either
end
• Ex: special sense organs (nose
and retina of eye)
• Multipolar
• Several dendrites and one axon
• Most common structure
• Ex: motor neurons and
interneurons
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Classification of Nerves
• Bundles of axons
• CNS: tract
• PNS: nerves
• PNS Classification
• Sensory (afferent) nerves
• Carry impulses towards the CNS
• Motor (efferent) nerves
• Carry impulses away from the CNS
• Mixed nerves
• Contains both sensory and motor fibers
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Nervous System Terminology
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Neuroglia (Glial Cells)
Cells that are non-conducting but support neurons
Types found in the PNS:
• Schwann cells (neurolemmocytes)
• Form myelin sheaths around peripheral axons
• Satellite cells (ganglionic gliocytes)
• Support cell bodies within the ganglia of the PNS
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Neuroglia (Glial Cells)
• Types found in the CNS
• Oligodendrocytes
• Forms myelin sheaths around CNS axons
• Microglia
• Migrates around CNS tissue and phagocytize foreign and
degenerated material
• Astrocytes
• Regulates neural external environment
• Forms the blood-brain-barrier between capillaries and neurons
• Ependymal cells
• Lines ventricles and secretes cerebrospinal fluid
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Neuroglia (Glial Cells)
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Myelination
• Provides myelination
• Increases rate of nerve
impulses
• Forms white matter
• PNS: Schwann Cells
• Gaps: nodes of Ranvier
• CNS: oligodendrocytes
• One oligodendrocyte
sends extensions to
several axons
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Blood-Brain Barrier
• Structural components:
• Tight junctions between endothelial cells
• Restricts paracellular (between cell) transport
• Movement is transcellular and selective
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Blood-Brain Barrier
• Molecules that can cross the BBB
• Nonpolar molecules (O2 and CO2)
• Organic molecules (alcohol, barbiturates, essential
amino acids)
• Ions and polar molecules (water, glucose)
• Requires channels and carrier proteins
• Ex: Glucose transport using GLUT1 carrier proteins
• Molecules that cannot cross the BBB
• Metabolic wastes
• Most drugs
• Challenge for treatment of brain diseases
• Proteins, nonessential amino acids
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Astrocytes & the BBB
• Influences interactions between neurons and
between neurons and blood
• Secretes regulatory molecules to produce:
• Tight junctions, carrier proteins, ion channels, enzymes to
destroy toxic molecules
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Electrical Activity in Axons
Excitability or Irritability
• Ability of neurons and muscle cells to change their
membrane potentials
• Caused by changes in permeability to ions
• Ions follow their electrochemical gradient
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Electrical Activity in Axons
Resting Membrane Potential
• Resting potential of -70 mV is
maintained by:
• Anions within the cell
• Na+/K+ pumps
• Permeability of the
membrane to positively
charged, inorganic ions (i.e.,
K+)
• Concentration of ions:
• High concentration of K+
inside the cell
• High concentration of Na+
outside the cell
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Electrical Activity in Axons
At rest, a neuron is polarized
• Inside is more negative
Changes in Membrane Potential:
• Depolarization
• Membrane potential becomes more positive
• Ex: positive ions enter the cell (i.e., Na+)
• Repolarization
• A return to resting potential
• Hyperpolarization
• Membrane potential becomes more negative
• Ex: positive ions leave the cell (i.e., K+) or negative ions enter
the cell (i.e., Cl-)
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Ion Channels
Changes in membrane potential are controlled by
changes in the flow of ions through channels
• Leakage Channels
• Always open
• Ex: K+ leakage channels
• Gated Channels
• Open: membrane more permeable
• Closed: membrane less permeable
• Types:
• Ligand Gated (Ex: Na+)
• Voltage Gated (Ex: Na+ and K+)
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Voltage-Gated Channels
• Closed at resting membrane
potential (-70 mV)
• Open by depolarization
• Na+ Channels
• Open: -55 mV
+
• K Channels
• Open: +30 mV
• Movement of ions due to
electrochemical gradient
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Generating an Action Potential
Depolarization
1. Stimulus causes dendritic membrane to
depolarize
• -70 mV (rest) à positive voltage
• If membrane potential reaches threshold (-55 mV) an
action potential occurs
2. Voltage-gated Na+ channels open at the axon
hillock
• Influx of Na+
• -55 mV à +30 mV
• Positive feedback
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Generating an Action Potential
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Generating an Action Potential
Repolarization
1. Voltage-gated Na+ channels become inactivated
• Decreases Na+ permeability
2. Voltage-gated K+ channels open
• +30 mV à -70 mV
• Efflux of K+
• Negative feedback
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Generating an Action Potential
Hyperpolarization
1. K+ efflux continues
• -70 mV à -85 mV
2. Voltage-gated K+ channels inactivated
Recovery
1. Voltage-gated channels closed
2. Resting membrane potential reestablished
• Na+/K+ pumps
• -85 mV à -70 mV
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Generating an Action Potential
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All-or-None Law
• If threshold is
reached à action
potential
• Stimulus intensity
does not affect
action potential
amplitude
Amplitude = Size of waveform
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Coding for Stimulus Intensity
• Increasing stimulus
intensity:
• Increases frequency
of action potentials
• Frequency modulated
• Activates more axon
fibers in a nerve
• Recruitment
Frequency = Number of occurrences/sec (Hz)
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Refractory Period
Absolute Refractory
Period
• Neuron incapable of
responding to stimulus
• Temporary
inactivation of voltagegated Na+ channels
• Makes a single AP
unidirectional!
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Refractory Period
Relative Refractory Period
• Some Na+ channels have
recovered
• Voltage-gated K+ channels
are still open
• A second AP is possible
but needs a greater
stimulus
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Cable Properties of Neurons
The ability of neurons to conduct
charges through their cytoplasm
• Poor due to:
• High internal resistance to the
spread of charges
• Leaking of charges through the
membrane
• Neurons cannot depend on cable
properties to move an impulse
down the length of an axon
• Change in potential would be
localized to 1-2 mm in length
• Some neurons are a meter or more
in length!
• Suggests neurons do not rely on cable
properties to propagate an AP!
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Conduction of Nerve Impulses
• AP initiates at the axon
hillock
• Voltage-gated Na+ channels
open
• Na+ efflux causes
depolarization
• The AP at one region serves
as the depolarization
stimulus for the next region
• Process continues along axon
length
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Action potentials travel in one direction
Action potentials only travel in
one direction!
• The temporary inactivation
of Na+ channels prevents the
AP from moving backwards!
• APs travel in only one
direction: from the axon
hillock à synaptic terminals
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Action Potentials & Dominoes
• All-or-none: 1st domino has to be pushed with enough force
(reach threshold) to knock down the row of dominoes
(action potential)
• Dominoes fall sequentially from one end to another similar
to an AP propagating down an axon
• Fallen dominoes represent the refractory period where an
axon cannot immediately initiate a new AP
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Conduction in an Unmyelinated Neuron
Action potentials produced
down the entire length of the
axon, at every patch of
membrane
• Slow conduction rate
• Many APs are generated, each
one an individual event
• Amplitude of each AP is the
same
• Conduction without decrement
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Conduction in a Myelinated Neuron
Saltatory Conduction:
Action potentials that
“leap” from node to node
• Myelin provides
insulation, improving the
speed of cable properties
• Nodes of Ranvier allow
Na+ and K+ to cross the
membrane every 1-2 mm
• Na+ ion channels are
concentrated at the node
• APs “leap” from node to
node
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Action Potential Conduction Speed
Increased by:
• Increased axon diameter
• Reduces resistance
• Myelination
• Saltatory conduction
• Ex:
• Thin, unmyelinated
neuron speed: 1.0m/sec
• Thick, myelinated neuron
speed 100m/sec
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Synapse
The functional connection
between a neuron and
second cell
• CNS: 2nd cell will be
another neuron
• PNS: 2nd cell will be a
neuron, muscle or gland
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Synapse
• Neuron-neuron connection: 1st neuron is the
presynaptic neuron and 2nd neuron is the postsynaptic
neuron
• Presynaptic neuron can signal the dendrite (axodendritic), cell
body (axosomatic), or axon (axoaxonic) of a second neuron
• Most synapses are axodendritic
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Synapse
Synaptic transmission can be electrical or chemical:
• Chemical
• Most common
• Neurotransmitters diffuse across synaptic cleft
• Electrical (gap junctions)
• Cells joined by gap junctions (connexin proteins)
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Electrical Synapse
• Location:
• Smooth & cardiac
muscle
• Between some
neurons in the brain
• Between glial cells
• Cells joined by gap
junctions (connexin
proteins)
• Allows ions and
molecules to pass
between cells
• Cells stimulated
together
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Chemical Synapse
• Transmission across
synaptic cleft
• Involves the release of
neurotransmitters (NTs)
from the presynaptic cell’s
terminal boutons
• NTs are stored in synaptic
vesicles
• Released via exocytosis
into the synaptic cleft
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Chemical Synapse
Process
1. AP reaches the terminal
bouton
2. Voltage-gated Ca2+ channels
open & Ca2+ influx
3. Ca2+ binds to synaptotagmin
(Ca2+ sensor)
4. Vesicles containing NT are
docked at the plasma
membrane by 3 SNARE
proteins
5. Ca2+ synaptotagmin complex
displaces part of the SNARE,
and the vesicle fuses
6. Pores form and release NT
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Actions of Neurotransmitter
Process
1. NTs (ligand) diffuses across the synaptic cleft and
binds to receptor proteins
2. Ion channels open, changing the membrane
potential
• Opening Na+ or Ca2+ channels results in a graded
depolarization: Excitatory Postsynaptic Potential (EPSP)
• Opening K+ or Cl- channels results in graded
hyperpolarization: Inhibitory Postsynaptic Potential
(IPSP)
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EPSP & IPSP
• EPSP
• Moves membrane potential
closer to threshold
• Produces a graded potential
• May require EPSPs from
several neurons to produce
an AP
• IPSP
• Moves membrane potential
further from threshold
• Inhibits an AP from forming
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EPSP
The inward flow of Na+
depolarizes the cell, creating
an EPSP
• EPSPs occur in dendrites
and cell bodies
• EPSPs can be summed to
produce a greater
depolarization (graded)
• If enough EPSPs are
summed to reach
threshold à stimulates
opening of voltage-gated
channels in the axon
hillock, leading to an AP
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EPSP
Summation:
• Spatial summation
• Simultaneous
stimulation by
several presynaptic
neurons
• All EPSPs and IPSPs
are added at the
axon hillock
• Temporal summation
• High frequency
stimulation by one
presynaptic neuron
• EPSPs add together
at the axon hillock
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Comparison of EPSPs and Action Potentials
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Actions of Neurotransmitter
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Chemically Regulated Channels
Binding of a NT to a receptor can open an ion channel in
one of two ways:
1. Ligand-gated channels
• Receptor protein is also the ion channel
• Binding of a NT directly to an ion channel, opens the channel
• Ex: Nicotinic ACh receptors
2. G-protein coupled channels
• NT receptor is separate from the protein that serves as the
ion channel
• Binding at the receptor opens ion channels indirectly by using
a G-protein
• Ex: Muscarinic ACh receptors, dopamine receptors,
norepinephrine receptors
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G-Protein Coupled Receptor
Process: G-proteins have 3 subunits ( , β, and ɣ)
1. Binding of ACh results in the dissociation of the subunit
2. The or the β – ɣ diffuses through the membrane to the ion
channel
3. The channel opens (or closes) for short period of time
4. The G-protein subunits dissociate from the channel and it closes
(opens)
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Neurotransmitter
Acetylcholine (ACh)
• Directly or indirectly opens ion channels when it
binds to its receptor
• Can be excitatory or inhibitory depending on the
organ involved:
• Excitatory
• CNS
• Some autonomic motor neurons
• All somatic motor neurons
• Inhibitory
• Some autonomic motor neurons
• Receptor Types: Nicotinic and Muscarinic
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ACh Receptors
Nicotinic ACh Receptors
• Ligand-gated channels
• Excitatory
• Locations:
• Motor end plate of skeletal
muscle cells
• Autonomic ganglia
• Some parts of the CNS
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ACh Receptors
Muscarinic ACh
Receptors
• G-protein coupled
receptors
• Excitatory (closed) or
Inhibitory (open)
• Locations:
• CNS
• Smooth and cardiac
muscles
• Glands innervated by
autonomic motor
neurons
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Agonists vs. Antagonists
1. Agonists: drugs that can stimulate a receptor
• Nicotine for nicotinic ACh receptors
• Muscarine for muscarinic ACh receptors
2. Antagonists: drugs that inhibit a receptor
• Curare is an antagonist for nicotinic ACh receptors
• Atropine is an antagonist for muscarinic ACh receptors
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Acetylcholinesterase (AChE)
AChE: enzyme that inactivates ACh
• ACh à acetate and choline
• ACh reuptake into presynaptic cell for reuse
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ACh in the PNS
• Somatic Nervous System
• Form neuromuscular junctions: synapses with skeletal
muscle fibers (motor end plate); contains nAChRs
• EPSPs: end-plate potentials
• Induces muscle contraction
• Autonomic Nervous System
• Neurons innervate cardiac muscles, smooth muscles in
blood vessels and visceral organs, and glands
• Parasympathetic
• Binding of ACh to receptors produces either EPSPs or IPSPs
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ACh in the PNS
Interruption of Neuromuscular Transmission
• Certain drugs can block neuromuscular
transmission
• Ex: Curare: antagonist of acetylcholine
• Blocks nACh receptors; muscles do not contract
• Leads to paralysis and death (due to paralyzed
diaphragm)
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ACh in the PNS
Other drugs that affect neural control of skeletal muscles
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ACh in the CNS
• Many cholinergic receptors in the brain
• Binding of ACh produces both EPSPs and IPSPs
• EPSPs due to nicotinic and muscarinic receptors
• IPSPs due to muscarinic receptors
• Ex: Alzheimer’s Disease
• Associated with loss of cholinergic neurons that synapse
on areas of the brain responsible for memory
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Neurotransmitter
Monoamines
• Regulatory molecules derived from amino acids
Types of Monoamines:
• Catecholamines
• Derived from tyrosine
• Includes: dopamine, norepinephrine, and epinephrine
• Serotonin
• Derived from L-tryptophan
• Histamine
• Derived from histidine
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Monoamines
• Monoamines bind to
g-protein coupled
receptors
• 2nd messenger
systems (i.e., cAMP)
• EPSPs and IPSPs
• Reuptake by
monoamine oxidase
(MAO)
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Monoamines: Catecholamines
• Utilizes G-protein receptors and 2nd messenger system
1. ⍺ subunit binds to adenylate cyclase; converts ATP à cAMP
2. cAMP activates protein kinase à phosphorylates other
proteins
3. Ion channel opens
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Monoamines: Catecholamines
Dopamine
• Dopaminergic neurons are found in the midbrain:
• Nigrostriatal dopamine system: motor control
• Ex: Parkinson’s Disease: Caused by degeneration of these
neurons. Patients treated with L-dopa and MAOIs (monoamine
oxidase inhibitors)
• Mesolimbic dopamine system: emotional reward
• Associated with drug addition (i.e., nicotine, alcohol, etc.)
• Ex: Schizophrenia is associated with too much dopamine in the
system. Patients treated with dopamine antagonists.
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Monoamines: Catecholamines
Norepinephrine
• Used in both CNS and PNS
• CNS: Brain regions associated with arousal
• PNS: Sympathetic neurons use this NT on smooth
muscles, cardiac muscles, and glands
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Monoamines: Serotonin
• Serotonergic neurons located in the raphe nuclei
(middle of brainstem)
• Multiple receptor types: diversity in function
• Different drugs target serotonin receptors
• Implicated in: mood, behavior, appetite, and
cerebral circulation
• Use in medicine
• LSD and hallucinogenic drugs are agonists
• Serotonin specific reuptake inhibitors (SSRIs) used to
treat depression (i.e., Prozac, Paxil, Zoloft)
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Neurotransmitter
Amino Acids
• Excitatory NTs
• Glutamic acid (common)
• Aspartic acid
• Inhibitory NTs
• GABA (common)
• Glycine
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Amino Acids
Excitatory NT: Glutamic Acid (Glutamate)
• Major excitatory NT in the brain
• Produces 80% EPSPs in the cerebral cortex
• Binds to ligand-gated receptors
• NMDA receptors, AMPA receptors, Kainate receptors
• NMDA and AMPA receptors work together in memory storage
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Amino Acids
Inhibitory: GABA
• Gamma-aminobutyric
acid: most common NT
in the brain
• Used by 1/3 of the
brain’s neurons
• Opens Cl− channels
• Involved in motor
control
• Degeneration of GABAsecreting neurons in the
cerebellum results in
Huntington’s disease
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Amino Acids
Inhibitory: Glycine
• NT produces IPSPs
• Opens Cl− channels, causing an influx of Cl−.
• Makes it harder to reach threshold
• Important in:
• Spinal cord: regulates skeletal muscle movement
• Relaxation of the diaphragm (necessary for breathing)
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Neurotransmitter
Neuropeptides
• Proteins that also serve as hormones or paracrine
signals
• NTs bind to G-coupled protein receptors
• Ex:
• Cholecystokinin (CCK): feeling of satiety
• Substance P: mediates sensations of pain
• Endogenous Opioids: pain relief and euphoria
• Neuropeptide Y: most abundant. Stress, circadian
rhythms, cardiovascular control, hunger stimulation
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Neurotransmitter
Endocannabinoids
• Short fatty acids produced in the dendrites and cell
bodies
• Released directly from the plasma membrane (no vesicle)
• NTs bind to the same receptors that bind THC (active
ingredient in marijuana)
• Functions in:
• Retrograde NTs released from the postsynaptic neuron
• Inhibits IPSP-producing NTs
• Involved in enhancing learning and memory and
inducing appetite
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Neurotransmitter
Gases
• Nitric Oxide
• Produced from the amino acid L-arginine
• Diffuses across membranes (no vesicle)
• May act as a retrograde NT
• PNS functions
• Involved in muscle relaxation
• Erection: Viagra works by increasing NO release
• Carbon Monoxide
• Used in the olfactory epithelium and cerebellum
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Neurotransmitter
ATP & Adenosine (Purines)
• Co-transmitters released via vesicles with another
NT
• Binds to purinergic receptors
• Functions
• Released with norepinephrine to stimulate
vasoconstriction and with ACh to stimulate intestinal
contraction
• ATP released by nonneural cells act as paracrine
regulators in blood clotting, taste, and pain
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