Transcript Neurotransmitters

PowerPoint® Lecture Slides
prepared by
Barbara Heard,
Atlantic Cape Community
Ninth Edition
College
Human Anatomy & Physiology
CHAPTER
11
Fundamentals
of the Nervous
System and
Nervous
Tissue: Part C
© Annie Leibovitz/Contact Press Images
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The Synapse
• Nervous system works because
information flows from neuron to neuron
• Neurons functionally connected by
synapses
– Junctions that mediate information transfer
• From one neuron to another neuron
• Or from one neuron to an effector cell
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Important Terminology
• Presynaptic neuron
– Neuron conducting impulses toward synapse
– Sends the information
• Postsynaptic neuron (in Pns may be a
neuron, muscle cell, or gland cell)
– Neuron transmitting electrical signal away
from synapse
– Receives the information
• Most function as both
PLAY
Animation: Synapses
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Figure 11.16 Synapses.
Axodendritic
synapses
Dendrites
Axosomatic
synapses
Cell body
Axoaxonal
synapses
Axon
Axon
Axosomatic
synapses
Cell body (soma)
of postsynaptic
neuron
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Synaptic Cleft
• Transmission across synaptic cleft
– Chemical event (as opposed to an electrical
one)
– Depends on release, diffusion, and receptor
binding of neurotransmitters
– Ensures unidirectional communication
between neurons
PLAY
Animation: Neurotransmitters
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Information Transfer Across Chemical
Synapses
• Neurotransmitter diffuses across synapse
• Binds to receptors on postsynaptic neuron
– Often chemically-gated ion channels
• Ion channels are opened
• Causes an excitatory or inhibitory event
(graded potential)
• Neurotransmitter effects terminated
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Termination of Neurotransmitter Effects
• Within a few milliseconds neurotransmitter
effect terminated in one of three ways
– Reuptake
• By astrocytes or axon terminal
– Degradation
• By enzymes
– Diffusion
• Away from synaptic cleft
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Figure 11.17 Chemical synapses transmit signals from one neuron to another using neurotransmitters.
Presynaptic
neuron
Presynaptic
neuron
Postsynaptic
neuron
1 Action potential
arrives at axon
terminal.
2 Voltage-gated Ca2+
channels open and Ca2+
enters the axon terminal.
3 Ca2+ entry
causes synaptic
vesicles to release
neurotransmitter
by exocytosis
Mitochondrion
Synaptic
cleft
Axon
terminal
Synaptic
vesicles
4 Neurotransmitter diffuses
across the synaptic cleft and
binds to specific receptors on
the postsynaptic membrane.
Postsynaptic
neuron
Ion movement
Enzymatic
degradation
Graded potential
Reuptake
Diffusion away
from synapse
5 Binding of neurotransmitter opens
ion channels, resulting in graded
potentials.
6 Neurotransmitter effects are
terminated by reuptake through
transport proteins, enzymatic
degradation, or diffusion away
from the synapse.
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Synaptic Delay
• Time needed for neurotransmitter to be
released, diffuse across synapse, and bind
to receptors
– 0.3–5.0 ms
• Synaptic delay is rate-limiting step of
neural transmission
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Postsynaptic Potentials
• Neurotransmitter receptors cause graded
potentials that vary in strength with
– Amount of neurotransmitter released and
– Time neurotransmitter stays in area
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Table 11.2 Comparison of Graded Potentials and Action Potentials (4 of 4)
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Postsynaptic Potentials
• Types of postsynaptic potentials
– EPSP—excitatory postsynaptic potentials
– IPSP—inhibitory postsynaptic potentials
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Excitatory Synapses and EPSPs
• Neurotransmitter binding opens chemically
gated channels
• Allows simultaneous flow of Na+ and K+ in opposite
directions
• Na+ influx greater than K+ efflux  net
depolarization called EPSP (not AP)
• EPSP help trigger AP if EPSP is of threshold
strength
– Can spread to axon hillock, trigger opening of
voltage-gated channels, and cause AP to be
generated
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Membrane potential (mV)
Figure 11.18a Postsynaptic potentials can be excitatory or inhibitory.
+30
0
Threshold
–55
–70
An EPSP is a local
depolarization of the
postsynaptic membrane
that brings the neuron
closer to AP threshold.
Neurotransmitter binding
opens chemically gated
ion channels, allowing
Na+ and K+ to pass
through simultaneously.
Stimulus
10
20
30
Time (ms)
Excitatory postsynaptic potential (EPSP)
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Inhibitory Synapses and IPSPs
• Reduces postsynaptic neuron's ability to
produce an action potential
– Makes membrane more permeable to K+ or
Cl–
• If K+ channels open, it moves out of cell
• If Cl- channels open, it moves into cell
– Therefore neurotransmitter hyperpolarizes cell
• Inner surface of membrane becomes more
negative
• AP less likely to be generated
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Membrane potential (mV)
Figure 11.18b Postsynaptic potentials can be excitatory or inhibitory.
+30
0
Threshold
An IPSP is a local
hyperpolarization of the
postsynaptic membrane
that drives the neuron
away from AP threshold.
Neurotransmitter binding
opens K+ or Cl– channels.
–55
–70
Stimulus
10
20
30
Time (ms)
Inhibitory postsynaptic potential (IPSP)
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Synaptic Integration: Summation
• A single EPSP cannot induce an AP
• EPSPs can summate to influence
postsynaptic neuron
• IPSPs can also summate
• Most neurons receive both excitatory and
inhibitory inputs from thousands of other
neurons
– Only if EPSP's predominate and bring to
threshold  AP
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Neurotransmitters
• Language of nervous system
• 50 or more neurotransmitters have been
identified
• Most neurons make two or more
neurotransmitters
– Neurons can exert several influences
• Usually released at different stimulation
frequencies
• Classified by chemical structure and by
function
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Classification of Neurotransmitters:
Chemical Structure
• Acetylcholine (ACh)
– First identified; best understood
– Released at neuromuscular junctions ,by
some ANS neurons, by some CNS neurons
– Synthesized from acetic and choline by
enzyme choline acetyltransferase
– Degraded by enzyme acetylcholinesterase
(AChE)
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Classification of Neurotransmitters:
Chemical Structure
• Biogenic amines
• Catecholamines
– Dopamine, norepinephrine (NE), and epinephrine
– Synthesized from amino acid tyrosine
• Indolamines
– Serotonin and histamine
– Serotonin synthesized from amino acid tryptophan;
histamine synthesized from amino acid histidine
• Broadly distributed in brain
– Play roles in emotional behaviors and biological clock
• Some ANS motor neurons (especially NE)
• Imbalances associated with mental illness
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Classification of Neurotransmitters:
Chemical Structure
• Gases and lipids - gasotransmitters
• Nitric oxide (NO), carbon monoxide (CO),
hydrogen sulfide gases (H2S)
• Bind with G protein–coupled receptors in the brain
• Lipid soluble
• Synthesized on demand
• NO involved in learning and formation of new
memories; brain damage in stroke patients,
smooth muscle relaxation in intestine
• H2s acts directly on ion channels to alter function
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Classification of Neurotransmitters:
Chemical Structure
– Endocannabinoids
• Act at same receptors as THC (active ingredient in
marijuana)
– Most common G protein-linked receptors in brain
•
•
•
•
Lipid soluble
Synthesized on demand
Believed involved in learning and memory
May be involved in neuronal development,
controlling appetite, and suppressing nausea
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Classification of Neurotransmitters:
Direct versus Indirect Actions
• Direct action
– Neurotransmitter binds to and opens ion
channels
– Promotes rapid responses by altering
membrane potential
– Examples: ACh and amino acids
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Figure 11.20 Direct neurotransmitter receptor mechanism: Channel-linked receptors.
Ion flow blocked
Ions flow
Ligand
Closed ion
channel
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Open ion
channel
Classification of Neurotransmitters: Direct
versus Indirect Actions
• Indirect action
– Neurotransmitter acts through intracellular
second messengers, usually G protein
pathways
– Broader, longer-lasting effects similar to
hormones
– Biogenic amines, neuropeptides, and
dissolved gases
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G Protein-Linked Receptors: Mechanism
• Second messengers
– Open or close ion channels
– Activate kinase enzymes
– Phosphorylate channel proteins
– Activate genes and induce protein synthesis
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Figure 11.21 Indirect neurotransmitter receptor mechanism: G protein–linked receptors.
Slide 8
Recall from Chapter 3 that G protein
signaling mechanisms are like a
molecular relay race.
Ligand (1st Receptor
messenger)
G protein
Enzyme
1 Neurotransmitter
(1st messenger) binds
and activates receptor.
2nd
messenger
Adenylate cyclase
Closed ion channel
Open ion channel
Receptor
G protein
5a cAMP changes membrane
permeability by opening or
closing ion channels.
5c cAMP activates
specific genes.
5b cAMP activates
GDP
enzymes.
2 Receptor
activates G
protein.
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3 G protein
activates
adenylate
cyclase.
4 Adenylate
cyclase converts
ATP to cAMP
(2nd messenger).
Active enzyme
Nucleus
Basic Concepts of Neural Integration
• Neurons function in groups
• Groups contribute to broader neural
functions
• There are billions of neurons in CNS
– Must be integration so the individual parts
fuse to make a smoothly operating whole
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Organization of Neurons: Neuronal Pools
• Functional groups of neurons
– Integrate incoming information received from
receptors or other neuronal pools
– Forward processed information to other destinations
• Simple neuronal pool
– Single presynaptic fiber branches and synapses with
several neurons in pool
– Discharge zone—neurons most closely associated
with incoming fiber
– Facilitated zone—neurons farther away from
incoming fiber
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Figure 11.22 Simple neuronal pool.
Presynaptic
(input) fiber
Facilitated zone
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Discharge zone
Facilitated zone
Types of Circuits
• Circuits
– Patterns of synaptic connections in neuronal
pools
• Four types of circuits
– Diverging
– Converging
– Reverberating
– Parallel after-discharge
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Figure 11.23a Types of circuits in neuronal pools.
Input
Many outputs
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Diverging circuit
• One input, many outputs
• An amplifying circuit
• Example: A single neuron in the
brain can activate 100 or more motor
neurons in the spinal cord and
thousands of skeletal muscle fibers
Figure 11.23b Types of circuits in neuronal pools.
Input 1
Input 2
Input 3
Output
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Converging circuit
• Many inputs, one output
• A concentrating circuit
• Example: Different sensory stimuli
can all elicit the same memory
Figure 11.23c Types of circuits in neuronal pools.
Input
Output
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Reverberating circuit
• Signal travels through a chain of
neurons, each feeding back to
previous neurons
• An oscillating circuit
• Controls rhythmic activity
• Example: Involved in
breathing, sleep-wake cycle,
and repetitive motor activities
such as walking
Figure 11.23d Types of circuits in neuronal pools.
Input
Output
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Parallel after-discharge
circuit
• Signal stimulates neurons
arranged in parallel arrays that
eventually converge on a
single output cell
• Impulses reach output cell at
different times, causing a burst
of impulses called an after-discharge
• Example: May be involved in
exacting mental processes
such as mathematical calculations
Patterns of Neural Processing:
Serial Processing
• Input travels along one pathway to a
specific destination
• System works in all-or-none manner to
produce specific, anticipated response
• Example – spinal reflexes
– Rapid, automatic responses to stimuli
– Particular stimulus always causes same
response
– Occur over pathways called reflex arcs
• Five components: receptor, sensory neuron,
CNS integration center, motor neuron, effector
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Figure 11.24 A simple reflex arc.
Stimulus
1 Receptor
Interneuron
2 Sensory neuron
3 Integration center
4 Motor neuron
5 Effector
Spinal cord (CNS)
Response
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Patterns of Neural Processing: Parallel
Processing
• Input travels along several pathways
• Different parts of circuitry deal
simultaneously with the information
– One stimulus promotes numerous responses
• Important for higher-level mental
functioning
• Example: a sensed smell may remind one
of an odor and any associated
experiences
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Developmental Aspects of Neurons
• Nervous system originates from neural
tube and neural crest formed from
ectoderm
• The neural tube becomes CNS
– Neuroepithelial cells of neural tube proliferate
to form number of cells needed for
development
– Neuroblasts become amitotic and migrate
– Neuroblasts sprout axons to connect with
targets and become neurons
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Axonal Growth: Finding the Target
• Growth cone at tip of axon interacts with its
environment via:
– Cell surface adhesion proteins (laminin, integrin, and
nerve cell adhesion molecules or N-CAMs) which
provide anchor points
– Neurotropins that attract or repel the growth cone
– Nerve growth factor (NGF) which keeps neuroblast
alive
• Once finds target must find right place to form
synapse
– Astrocytes provide physical support and cholesterol
essential for construction of synapses
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Figure 11.25 A neuronal growth cone.
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Cell Death
• About 2/3 of neurons die before birth
– If do not form synapse with target
– Many cells also die due to apoptosis
(programmed cell death) during development
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