Title: Signal Transmission Between the Neurons
1Section 2 Signal Transmission Between the Neurons
2 Neurotransmission
-
- 1.Chemical synapse (Classical Synapse)
- Predominates in the vertebrate nervous system
- 2.Non-synaptic chemical transmission
- 3.Electrical synapse
- Via specialized gap junctions
- Does occur, but rare in vertebrate NS
- Astrocytes can communicate via gap junctions
3Chemical Synapse
- Terminal bouton is separated from postsynaptic
cell by synaptic cleft. - Vesicles fuse with axon membrane and NT released
by exocytosis. - Amount of NTs released depends upon frequency of
AP.
4 Non-synaptic chemical transmission
The postganglionic neurons innervate the smooth
muscles. ? No recognizable endplates or other
postsynaptic specializations ? The multiple
branches are beaded with enlargements
(varicosities) that are not covered by Schwann
cells and contain synaptic vesicles
Fig. Ending of postganglionic autonomic neurons
on smooth muscle
5Non-synaptic chemical transmission continued
? In noradrenergic neurons, the varicosities are
about 5?m, with up to 20,000 varicosities per
neuron ? Transmitter is apparently released at
each varicosity, at many locations along each
axon ? One neuron innervate many effector cells.
Fig. Ending of postganglionic autonomic neurons
on smooth muscle
6Electrical 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.
7Electrical Synapses
- Electric current flow- communication takes place
by flow of electric current directly from one
neuron to the other - No synaptic cleft or vesicles cell membranes in
direct contact - Communication not polarized- electric current can
flow between cells in either direction
8Chemical Synapse
Electrical Synapse
Purves, 2001
9I The Chemical Synapse and Signal Transmission
10- The chemical synapse is a specialized junction
that transfers nerve impulse information from a
pre synaptic membrane to a postsynaptic membrane
using neurotransmitters and enzymes
11Synaptic connections
- 100,000,000,000 neurons in human brain
- Each neuron contacts 1000 cells
- Forms 10,000 connections/cell
- How many synapses?
12- Neurotransmitter- communication via a chemical
intermediary called a neurotransmitter, released
from one neuron and influences another - Synaptic cleft- a small gap between the sending
(presynaptic) and the receiving (postsynaptic)
site
Chemical Synapses
13- Synaptic vesicles- small spherical or oval
organelles contain chemical transmitter used in
transmission - Polarization- communication occurs in only one
direction, from sending presynaptic site, to
receiving postsynaptic site
Chemical Synapses
141. Synaptic Transmission Model
- Precursor transport
- NT synthesis
- Storage
- Release
- Activation
- Termination diffusion, degradation, uptake,
autoreceptors
15Postsynaptic Membrane
Presynaptic Axon Terminal
Terminal Button
Dendritic Spine
16(1) Precursor Transport
17(2) Synthesis
enzymes/cofactors
18(3) Storage
in vesicles
19Terminal Button
Dendritic Spine
Synapse
20(4) Release
Terminal Button
Dendritic Spine
Synapse
Receptors
21Terminal Button
Dendritic Spine
AP
Synapse
22Exocytosis
Ca2
23Each vesicle contains one quanta of
neurotransmitter (approximately 5000 molecules)
quanta release
24(5) Activation
25(6) Termination
26(6.1) Termination by... Diffusion
27(6.2) Termination by... Enzymatic degradation
28(6.3) Termination by... Reuptake
29(6.4) Termination by... Autoreceptors
A
30Autoreceptors
- On presynaptic terminal
- Binds NT
- same as postsynaptic receptors
- different receptor subtype
- Decreases NT release synthesis
- Metabotropic receptors
31Synaptic Transmission
- 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.
32Synaptic Transmission (continued)
- 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.
- EPSP depolarization.
- IPSP hyperpolarization.
- Neurotransmitter inactivated to end transmission.
332 EPSP and IPSP
34- (1)Excitatory postsynaptic potential (EPSP)
- An AP arriving in the presynaptic terminal cause
the release of neurotransmitter - ?The molecules bind and active receptor on the
postsynaptic membrane -
35- (1)Excitatory postsynaptic potential (EPSP)
- Opening transmitter-gated ions channels ( Na)
in postsynaptic- membrane - Both an electrical and a concentration gradient
driving Na into the cell - The postsynaptic membrane will become
depolarized(EPSP). -
36EPSP
- No threshold.
- Decreases resting membrane potential.
- Closer to threshold.
- Graded in magnitude.
- Have no refractory period.
- Can summate.
37(2) Inhibitory postsynaptic potential (IPSP) A
impulse arriving in the presynaptic terminal
causes the release of neurotransmitter The
molecular bind and active receptors on the
postsynaptic membrane open CI- or, sometimes K
channels More CI- enters, K outer the cell,
producing a hyperpolarization in the postsynaptic
membrane.
38- (IPSPs)
- No threshold.
- Hyperpolarize postsynaptic membrane.
- Increase membrane potential.
- Can summate.
- No refractory period.
39(No Transcript)
403 Synaptic Inhibition
- Presynaptic inhibition
- Amount of excitatory NT released is decreased by
effects of second neuron, whose axon makes
synapses with first neurons axon. - Postsynaptic inhibition
41(1) Postsynaptic inhibition
- Concept effect of inhibitory synapses on the
postsynaptic membrane. - Mechanism IPSP, inhibitory interneuron
- Types
- ?Afferent collateral inhibition( reciprocal
inhibition) - ?Recurrent inhibition.
42- 1) Reciprocal inhibition
- Activity in the afferent fibers from the muscle
spindles (stretch receptors) excites (EPSPs)
directly the motor neurons supplying the muscle
from which the impulses come. -
Postsynaptic inhibition
At the same time, inhibits (ISPSs) those motor
neurons supplying its antagonistic muscles.
43 1) Reciprocal inhibition The latter response is
mediated by branches of the afferent fibers that
end on the interneurons.
Postsynaptic inhibition
The interneurons, in turn, secrete the inhibitory
transmitter (IPSP) at synapses on the proximal
dendrites or cell bodies of the motor neurons
that supply the antagonist.
44Neurons may also inhibit themselves in a negative
feedback fashion. Each spinal motor neuron
regularly gives off a recurrent collateral that
synapses with an inhibitory interneuron which
terminates on the cell body of the spinal neuron
and other spinal motor neurons. The inhibitory
interneuron to secrete inhibitory mediator, slows
and stops the discharge of the motor neuron.
Postsynaptic inhibition
2) Recurrent inhibition
45Concept the inhibition occurs at the presynaptic
terminals before the signal ever reaches the
synapse. The basic structure an axon-axon
synapse (presynaptic synapse), A and B. Neuron A
has no direct effect on neuron C, but it exert a
Presynaptic effect on ability of B to Influence
C. The presynatic effect May decrease the amount
of neuro- transmitter released from B
(Presynaptic inhibition) or increase it
(presynaptic facilitation).
(2) Presynaptic inhibition
B
A
A
A
B
C
C
46Presynaptic inhibition
The mechanisms Activation of the
presynaptic receptors increases CI- conductance,
? to decrease the size of the AP reaching the
excitatory ending, ? reduces Ca2 entry and
consequently the amount of excitatory transmitter
decreased.
Voltage-gated K channels are also opened, and
the resulting K efflux also decreases the Ca2
influx.
47Presynaptic Inhibition
Excitatory Synapse
- A active
- B more likely to fire
- Add a 3d neuron
48Presynaptic Inhibition
Excitatory Synapse
- Axon-axon synapse
- C is inhibitory
49Presynaptic Inhibition
Excitatory Synapse
- C active
- less NT from A when active
- B less likely to fire
504 Synaptic Facilitation Presynaptic and
Postsynaptic
51(1) Presynaptic Facilitation
Excitatory Synapse
- A active
- B more likely to fire
52Presynaptic Facilitation
Excitatory Synapse
- C active (excitatory)
- more NT from A when active (MechanismAP of A is
prolonged and Ca 2 channels are open for a
longer period.) - B more likely to fire
53(2) Postsynaptic facilitation neuron that has
been partially depolarized is more likely to
undergo AP.
54EPSP
- Depolarization
- more likely to fire
Vm
-65mv
- 70mv
AT REST
-
Time
555 Synaptic Integration
- EPSPs can summate, producing AP.
- Spatial summation
- Numerous PSP converge on a single postsynaptic
neuron (distance). - Temporal summation
- Successive waves of neurotransmitter release
(time).
56(1) Spatial Summation
- The accumulation of neurotransmitter in the
synapse due the combined activity of several
presynaptic neurons entering the Area (Space) of
a Convergent Synapse. - A space (spatial) dependent process.
57Spatial Summation
vm
-65mv
- 70mv
AT REST
-
Time
58(2) Temporal Summation
- The accumulation of neurotransmitters in a
synapse due to the rapid activity of a
presynaptic neuron over a given Time period. - Occurs in a Divergent Synapse. (explain later)
- Is a Time (Temporal) dependent process.
59Temporal Summation
- Repeated stimulation
- same synapse
Vm
-65mv
- 70mv
AT REST
-
Time
60(3) EPSPs IPSPs summate
- CANCEL EACH OTHER
- Net stimulation
- EPSPs IPSPs net effects
61EPSP IPSP
- 70mv
626. Divergent and Convergent Synapse
63Divergent Synapse
- A junction that occurs between a presynaptic
neuron and two or more postsynaptic neurons
(ratio of pre to post is less than one).
- The stimulation of the postsynaptic neurons
depends on temporal summation).
64Convergent Synapse
- A junction between two or more presynaptic
neurons with a postsynaptic neuron (the ratio of
pre to post is greater than one). - The stimulation of the postsynaptic neuron
depends on the Spatial Summation.
Presynaptic neurons
Postsynaptic neuron
65II Neurotransmitters and receptors
66 1. Basic Concepts of NT and receptor
Neurotransmitter Endogenous signaling molecules
that alter the behaviour of neurons or effector
cells. Neuroreceptor Proteins on the cell
membrane or in the cytoplasm that could bind with
specific neurotransmitters and alter the behavior
of neurons of effector cells
67- Vast array of molecules serve as
neurotransmitters - The properties of the transmitter do not
determine its effects on the postsynaptic cells - The properties of the receptor determine whether
a transmitter is excitatory or inhibitory
68A neurotransmitter must (classical definition)
- Be synthesized and released from neurons
- Be found at the presynaptic terminal
- Have same effect on target cell when applied
externally - Be blocked by same drugs that block synaptic
transmission - Be removed in a specific way
Purves, 2001
69Classical Transmitters (small-molecule
transmitters)
Non-classical Transmitters
- Biogenic Amines
- Acetylcholine
- Catecholamines
- Dopamine
- Norepinerphrine
- Epinephrine
- Serotonin
- Amino Acids
- Glutamate
- GABA (?-amino butyric acid)
- Glycine
- Neuropeptides
- Neurotrophins
- Gaseous messengers
- Nitric oxide
- Carbon Monoxide
- D-serine
70Agonist A substance that mimics a specific
neurotransmitter, is able to attach to that
neurotransmitter's receptor and thereby produces
the same action that the neurotransmitter usually
produces. Drugs are often designed as receptor
agonists to treat a variety of diseases and
disorders when the original chemical substance is
missing or depleted.
71Antagonist Drugs that bind to but do not activate
neuroreceptors, thereby blocking the actions of
neurotransmitters or the neuroreceptor agonists.
72- Same NT can bind to different -R
- different part of NT
73Specificity of drugs
Drug B
Drug A
74Five key steps in neurotransmission
- Synthesis
- Storage
- Release
- Receptor Binding
- Inactivation
Purves, 2001
75Synaptic vesicles
- Concentrate and protect transmitter
- Can be docked at active zone
- Differ for classical transmitters (small,
clear-core) vs. neuropeptides (large, dense-core)
76Neurotransmitter Co-existence (Dale
principle) Some neurons in both the PNS and CNS
produce both a classical neurotransmitter (ACh or
a catecholamine) and a polypeptide
neurotransmitter. They are contained in different
synaptic vesicles that can be distinguished using
the electron microscope. The neuron can thus
release either the classical neurotransmitter or
the polypeptide neurotransmitter under different
conditions.
77Purves, 2001
78Receptors determine whether
- Synapse is excitatory or inhibitory
- NE is excitatory at some synapses, inhibitory at
others - Transmitter binding activates ion channel
directly or indirectly. - Directly
- ionotropic receptors
- fast
- Indirectly
- metabotropic receptors
- G-protein coupled
- slow
792. Receptor Activation
- Ionotropic channel
- directly controls channel
- fast
- Metabotropic channel
- second messenger systems
- receptor indirectly controls channel
80(1) Ionotropic Channels
neurotransmitter
NT
81Ionotropic Channels
82Ionotropic Channels
NT
83Ionotropic Channels
84(2) Metabotropic Channels
- Receptor separate from channel
- G proteins
- 2d messenger system
- cAMP
- other types
- Effects
- Control channel
- Alter properties of receptors
- regulation of gene expression
85(2.1) G protein direct control
- NT is 1st messenger
- G protein binds to channel
- opens or closes
- relatively fast
86G protein direct control
87G protein direct control
Pore
88(2.2) G protein Protein Phosphorylation
external signal nt
external signal NT
norepinephrine
GS
2d messenger
2d messenger
cAMP
secondary effector
secondary effector
protein kinase
89G protein Protein Phosphorylation
PK
90G protein Protein Phosphorylation
ATP
cAMP
PK
91G protein Protein Phosphorylation
ATP
P
cAMP
PK
92(3) Transmitter Inactivation
- Reuptake by presynaptic terminal
- Uptake by glial cells
- Enzymatic degradation
- Presynaptic receptor
- Diffusion
- Combination of above
93Summary of SynapticTransmission
Purves,2001
94Basic Neurochemistry
953. Some Important Transmitters
96(1) Acetylcholine (ACh) as NT
97Acetylcholine Synthesis
choline
acetyl CoA
98Acetylcholinesterase (AChE)
- Enzyme that inactivates ACh.
- Present on postsynaptic membrane or immediately
outside the membrane. - Prevents continued stimulation.
99(No Transcript)
100The Life Cycle of Ach
101Ach - Distribution
- Peripheral N.S.
- Excites somatic skeletal muscle (neuro-muscular
junction) - Autonomic NS
- Ganglia
- Parasympathetic NS--- Neuroeffector junction
- Few sympathetic NS Neuroeffector junction
- Central N.S. - widespread
- Hippocampus
- Hypothalamus
102Ach Receptors
- ACh is both an excitatory and inhibitory NT,
depending on organ involved. - Causes the opening of chemical gated ion
channels. - Nicotinic ACh receptors
- Found in autonomic ganglia (N1) and skeletal
muscle fibers (N2). - Muscarinic ACh receptors
- Found in the plasma membrane of smooth and
cardiac muscle cells, and in cells of particular
glands .
103Acetylcholine Neurotransmission
- Nicotinic subtype Receptor
- Membrane Channel for Na and K
- Opens on ligand binding
- Depolarization of target (neuron, muscle)
- Stimulated by Nicotine, etc.
- Blocked by Curare, etc.
- Motor endplate (somatic) (N2),
- all autonomic ganglia, hormone producing cells of
adrenal medulla (N1)
104Acetylcholine Neurotransmission
- Muscarinic subtype Receptor M1
- Use of signal transduction system
- Phospholipase C, IP3, DAG, cytosolic Ca
- Effect on target cell specific (heart ?, smooth
muscle intestine ?) - Blocked by Atropine, etc.
- All parasympathetic target organs
- Some sympathetic targets (endocrine sweat glands,
skeletal muscle blood vessels - dilation)
105Acetylcholine Neurotransmission
- Muscarinic subtype M2
- Use of signal transduction system
- via G-proteins, opens K channels, decrease in
cAMP levels - Effect on target cell specific
- CNS
- Stimulated by ?
- Blocked by Atropine, etc.
106Cholinergic Agonists
- Direct
- Muscarine
- Nicotine
- Indirect
- AChE Inhibitors
107Cholinergic Antagonists
- Direct
- Nicotinic - Curare
- Muscarinic - Atropine
-
108Ligand-Operated ACh Channels
N Receptor
109G Protein-Operated ACh Channel
M receptor
110(2) Monoamines as NT
111Monoamines
- Catecholamines
- Dopamine - DA
- Norepinephrine - NE
- Epinephrine - E
- Indolamines -
- Serotonin - 5-HT
112Mechanism of Action (? receptor)
113Epi
a1
G protein
PLC
IP3
Ca2
114Norepinephrine (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.
115(No Transcript)
116Adrenergic Neurotransmission
- ?1 Receptor
- Stimulated by NE, E,
- blood vessels of skin, mucosa, abdominal viscera,
kidneys, salivary glands - vasoconstriction, sphincter constriction, pupil
dilation
117Adrenergic Neurotransmission
- ?2 Receptor
- stimulated by, NE, E, ..
- Membrane of adrenergic axon terminals
(pre-synaptic receptors), platelets - inhibition of NE release (autoreceptor),
- promotes blood clotting, pancreas decreased
insulin secretion
118Adrenergic Neurotransmission
- ?1 receptor
- stimulated by E, .
- Mainly heart muscle cells,
- increased heart rate and strength
119Adrenergic Neurotransmission
- ? 2 receptor
- stimulated by E ..
- Lungs, most other sympathetic organs, blood
vessels serving the heart (coronary vessels), - dilation of bronchioles blood vessels
(coronary vessels), relaxation of smooth muscle
in GI tract and pregnant uterus
120Adrenergic Neurotransmission
- ? 3 receptor
- stimulated by E, .
- Adipose tissue,
- stimulation of lipolysis
121(3) Amino Acids as NT
- Glutamate acid and aspartate acid
- Excitatory Amino Acid (EAA)
- gamma-amino-butyric acid (GABA) and glycine
- Inhibitory AA
122(4) Polypeptides as NT
- CCK
- Promote satiety following meals.
- Substance P
- Major NT in sensations of pain.
123(5) Monoxide Gas NO and CO
- Nitric Oxide (NO)
- Exerts its effects by stimulation of cGMP.
- Involved in memory and learning.
- Smooth muscle relaxation.
- Carbon monoxide (CO)
- Stimulate production of cGMP within neurons.
- Promotes odor adaptation in olfactory neurons.
- May be involved in neuroendocrine regulation in
hypothalamus.