Nazli Karimi; MD , PHD.
Baskent University Physiology Compartment Ankara
Neurotransmitter
 Neurotransmitters are often referred to as the body’s
chemical messengers. They are the molecules used
by the nervous system to transmit messages
between neurons, or from neurons to muscles.
Neurotransmitter Types
 Small molecules transmitter substances:
Small transmitters action quickly when they released from
axon terminal.
 Class I: Acetylcholine
 Class II(Biogenic Amines): Dopamine, Norepinephrine,
Serotonin,Histamine
 Class III (Amino Acids): Glutamate, Aspartate, γAminobutyric acid (GABA), Glycine
 Class IV: Nitric oxide (NO), Carbon monoxide (CO)
Neurotransmitters
 Large molecules
transmitter substances:
 Neuropeptide
(substance P,
enkephalin,
vasopressin)
Acetylcholine or ACh
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Location
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primarily in brain, spinal cord
target organs of autonomic nervous system
Two kinds of receptors
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Indicated effects:
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Nicotinic:
nicotine stimulates
Excitatory; found predominately on neuromuscular junctions
Muscarinic
Muscarine (mushroom derivative) stimulates
Both excitatory AND Inhibitory; found predominately in brain
excitation or inhibition of target organs
essential in movement of muscles
important in learning and memory
Too much: muscle contractions- e.g. atropine poisoning
Too little: paralysis: curarae and botulism toxin
Norepinephrine or NE
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Called epinephrine in peripheral nervous system
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Also a hormone in peripheral system: adrenalin
Chemically extremely similar to Dopamine, serotonin
Located in
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brain, spinal cord
certain target organs (heart, lungs)
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At least two kinds: NE alpha and NE beta
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Indicated effects:
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Primarily excitatory
Fear/flight/fight system
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Too much: overarousal, mania, cardiac issues
Too little: underarousal, depression, cardiac issues
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NE
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Location:
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Dopamine or DA
primarily in brain
frontal lobe, limbic system, substania nigra
Indicated effects:
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inhibitory: reduces chances of action potential
involved in voluntary movement, emotional arousal
reward learning and motivation to get reward
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Critical for modulating movement and reward motivation
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Primary task is to inhibit unwanted movement
Responsible for motivation to get reward: movement and initiative
Too little: Parkinson's disease:
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Treatment: INCREASE available DA via L-Dopa
Too much: schizophrenia
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Treatment: REDUCE available DA via antidopaminergics/antipsychotics
Serotonin or 5HT
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Located in brain and spinal cord
5-hydroxy-tryptomine
Lots of 5HT receptors in the gut!
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Indicated effects
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Both inhibition and excitation
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Important in depression, sleep, digestion and emotional arousal
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chemically very similar to NE and DA
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Too little is linked to depression and sleep disorders
 Too much: Serotonin syndrome: confusion, twitching and trembling, dilated pupils,
shivering, goosebumps, headache, sweating and diarrhea., irregular and fast heartbeat
• Many antidepressants are specific to this NT
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SSRI’s
Block reuptake of 5HT in the synapse
Amino Acids
• Gamma-aminobutryic Acid or GABA
– Predominant inhibitory NT
– GABA deficiency related to epilepsy, seizure disorders
Too much: oversedation, over-relaxing of muscles
(including heart, respiration)
Too little: anxiety!
Amino Acids
 Glutamate:
– Principal excitatory NT in central nervous system
– Critical for learning: it is Glutamate and the NMDA
receptors that allow for long term potentiation
 Glycine:
– Inhibitory NT in spinal cord and lower brain (brain
stem)
– Regulates motor activity by inhibiting unwanted
movement
Neuromodulators:
Neuropeptides and Gases
• Neuromodulators:
• do not directly excite or inhibit postsynaptic neuron
• increase or decrease release of NT by altering response of postsynaptic
cells to various inputs
• In a way, are helpers to neurotransmitters
• Peptides = chains of amino acids
– Endorphins: related to regulation of pain and feeling of
reinforcement
– Substance P: transmitter involved in sensitivity to pain;
Neuropeptide Y: critical for regulating metabolic functions,
especially eating
 Gases such as Nitric Oxide:
– serves as retrograde NT (that is, a backwards NT)
– influences presysnaptic membrane’s release of NT
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Viagra: increases nitric oxide’s ability to relax blood vessels
Again: Three Steps for firing
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Resting potential: voltage is about -70mV
– Dendrites receive incoming signals
– If sufficient, cell goes into firing mode
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Action potential
– Voltage changes from -70mV to +40mV
– Ions exchange places
– Repeats itself rapidly down axon
Refractory Period:
– below resting or lower than -70mV
– Cell recovers from firing
– Absolute refractor period: Brief time period when cannot fire again
– Relative refractory period: Brief time period when difficult for it to fire
again.
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The Neuron Fires
 Action potential causes nearby Na+ channels to open, so another
action potential is triggered right next to first one, and this
continues all the way down the axon
 Chain reaction
 Action potential ≠ local potential in several important ways:
 Local potential = graded potential- it varies in magnitude depending
on strength of stimulus that produced it; action potential is ungraded
 Action potential obeys all or none law: occurs at full strength or not at
all
 Action potential is nondecremental: does NOT lose strength at each
successive point (local potentials do degrade)
Neurons Communicate at Synapses
Synapse
 The region where an axon
terminal meets its target cell is
called a synapse.
 The neuron that delivers a
signal to the synapse is known
as the presynaptic cell, and
the cell that receives the signal
is called the postsynaptic
cell.
 The narrow space between the
two cells is called the
synaptic cleft.
Synaps
 A synapse is the functional connection between a neuron and
the cell it is signaling
 In the CNS, this second cell will be another neuron.
 A presynaptic neuron can signal the dendrite, cell body, or axon
of a second neuron.
 There are axodendritic, axosomatic, and axoaxonic synapses.
 Most synapses are axodendritic and are 1 direction
 In the PNS, the second cell will be in a muscle or gland; often
called myoneural or neuromuscular junctions
 Synapses can be electrical or chemical
Electrical Synapses
 Electrical synapses occur in
smooth muscle and cardiac
muscle, between some
neurons of the brain, and
between glial cells.
 Cells are joined by gap
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junctions.
Channel
Connexon-formed by six
connexins
Cells are said to be “electrically
coupled”
Flow of ions from cytoplasm to
cytoplasm
Electrical Synapses
 Stimulation causes
phosphorylation or
dephosphorylation of
connexin proteins to
open or close the
channels
Electrical Synapses
 Very fast transmission
 Postsynaptic potentials
(PSPs)
 Synaptic integration: Several
PSPs occurring
simultaneously to excite a
neuron (i.e. causes AP)
Chemical Synapses
 Most synapses involve the
release of a chemical called a
neurotransmitter from the
axon’s terminal boutons.
 The synaptic cleft is very
small, and the presynaptic
and postsynaptic cells are
held close together by cell
adhesion molecules (CAMs).
One – Way Conduction: At chemical synapses, conduction of
impulses occurs in one direction only; from the presynaptic to the
postsynaptic neurons & not in the opposite direction.
Neurotransmitter Synthesis and Storage
Synthesis of peptide
neurotransmitters
Synthesis of amine
and amino acids
Release of Neurotransmitter
Neurotransmitter Recovery and
Degradation
 Neurotransmitters must be cleared from the
synapse to permit another round of synaptic
transmission.
 Methods:
 Diffusion
 Enzymatic degradation in the synapse.
 Presynaptic reuptake followed by degradation or
recycling.
 Uptake by glia
 Uptake by the postsynaptic neuron and
desensitization.
Two basic kinds of Neurotransmitters
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Excitatory:
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Inhibitory:
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create Excitatory postsynaptic potentials: EPSP's
stimulate or push neuron towards an action potential
Create Inhibitory postsynaptic potentials: IPSP's
Reduce probability that neuron will show an action potential
Some neurotransmitters are both inhibitory and excitatory,
depending upon situation and location and type of
reseptores.
Action in the Synapse
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Neurotransmitter is released into the
synapse
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diffuses across synapse to next neuron’s dendrite
This “next dendrite” is post-synaptic
Neurotransmitter is attracted to the POSTsynaptic side:
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receptor sites on the next neurons dendrites
neurotransmitter must match molecular shape of
receptor site
Activation of receptor causes ion channels in
membrane to open or activate some biochemical
reactions in postsynaptic cells
EPSPs and IPSPs
 EPSPs move the membrane potential closer to
threshold; may require EPSPs from several neurons to
actually produce an action potential
 IPSPs move the membrane potential farther from
threshold.
 Can counter EPSPs from other neurons so summation
of EPSPs and IPSPs at the initial segment of the axon
(next to the axon hillock) determines whether an
action potential occurs.
Excitatory Postsynaptic Potential (EPSP)
Inhibitory Postsynaptic Potential (IPSP)
Inhibitory Neurotransmitters:
Glycine and GABA
Graded Potential
 When ligand-gated ion channels open, the membrane
potential changes depending on which ion channel is
open.
 a)Opening Na+or Ca2+ channels results in a graded
depolarization called an excitatory postsynaptic
potential (EPSP).
 b)Opening K+or Cl−channels results in a graded
hyperpolarization called inhibitory postsynaptic
potential (IPSP).
Two kinds of Receptor Action
 Ionotropic receptors
 Receptor-channels
 Mediate rapid responses
 Alter ion flow across membranes
 Metabotropic receptors
 G protein–mediated receptors
 Mediate slower responses
 Some open or close ion channels
G Protein-Coupled Receptors
 Structure: Receptor protein with a
ligand binding domain and connected
to G –protein consisting of an alpha,
beta and gama subunit.
 Activation: 1) Ligand binds to receptor;
2) Receptor activates G-protein; 3) Gprotein dissociated; 4) alpha subunit
activates an effector protein.
 Effectors G-proteins act in one of two
ways:
 By opening ion channels
 By activating enzymes that
synthesize second-messenger
molecules.
 Tend to be slower, longer lasting and
have greater diversity than ligand gated
ion channels.
Neural Integration
 Divergence/convergence
 Summation
 The summing of input from various synapses at the axon
hillock of the postsynaptic neuron to determine whether
the neuron will generate action potentials or not.
Synaptic Integration
 Each neuron may receive thousands of inputs in
the form of ion channel and G-coupled protein
activation.
 These complex inputs give rise to simple output in
the form of action potentials.
 Neural computation
 Neurotransmitters are released
 EPSP and IPSP Summation
 Neurons do sophisticated computations by adding
together EPSPs and IPSP to produce a significant
postsynaptic depolarization.
 Types of Summation: Spatial and Temporal Summation.
Spatial Summation
A neuron may receive greater than 10, 000 inputs from presynaptic
neurons.
The initiation of an action potential from several simultaneous
subthreshold graded potentials, originating from different
locations, is known as spatial summation.
Temporal Summation
When summation occurs from graded potentials overlapping in
time, it is called temporal summation.
Autoreceptors and Presynaptic Inhibition
 Receptors are
sometimes found on the
presynaptic terminal.
 Activation leads to:
 Inhibition of
neurotransmitter release
 Neurotransmitter
synthesis.
 Autoreceptors may act
as a brake on the release
of neurotransmitters.