Electrical
• 2 neurons linked together by gap junctions
• Function in nervous system:
- rapid communication
- bidirectional communication
- excitation/inhibition at the same synapse
• Some between neurons and glia cells
Chemical
• Signal transduction
• Excitatory
• Inhibitory
• Slower communication
• Unidirectional communication

Recall where chemical synapses are found?

Communication
Across a Synapse
1. Action Potential
2. Voltage-gated Ca channels open
3. Ca triggers exocytosis
4. Nt diffuses and binds to receptor
5. Response in cell
Response is terminated by removing nt from synaptic cleft
6. Degradation
7.
Reuptake
8.
Diffusion

•
Rate of the response is due to the mechanism by which the signal is received and transferred at the plasma membrane.
•
Fast responses at ionotropic receptors
(channel-linked) .
•
Slow responses at metabotropic receptors
(G-protein-linked).

•
The receptor is a ligand-gated ion channel.
•
Ligand binding directly opens ion channel.
•
Fast action, short latency between nt binding and response.
•
Response is brief.

Ionotropic Receptors
•
5 subunits form the pore through the membrane.
•
Binding of ligand opens the pore.
• Ions flow into or out of the cell.
•
Produces EPSP or IPSP
(depending on the ion channel).
•
Rapid desensitization (loss of activity) if continuously exposed to nt.
•
Limits postsynaptic responding when presynaptic neurons are highly active for a period of time.

High
Ion Flow
Ionotropic Receptors
Sensitization
Low
Time, ms, in exposure to neurotransmitter

•
Can have multiple binding sites for various neuromodulators.
•
Can enhance or inhibit binding of endogenous ligands.
•
Are good targets for drugs.

Fast Responses at Ionotropic
Receptors

•
Most common type of receptor.
•
Coupled to G protein.
•
No direct control of ion channels.
•
Second messengers.

•
Single subunit with 7 transmembrane spanning domains.
• Highly conserved across the “receptor superfamily”.
•
Ligand binds in cleft on external face.
•
Ligand binding activates G protein
•
G protein activate various effectors.
•
Sometimes the effectors are the ion channels.

β-adrenergic receptor
NE +
Extracellular space
4) The GTP-bound α of the G s s s protein results in a s
, residue on the 3 rd s trimeric G the α s s protein complex. subunit can remain active again for next step)
C
Cytoplasm i3 loop
GTP
G s protei n cAMP
GDP cAMP cAMP cAMP
ATP

Slow Responses at Metabotropic
Receptors: Direct G-Protein Coupling

Slow Responses at Metabotropic
Receptors: Second Messenger Coupling

• Change in membrane potential in response to neurotransmitter binding to receptor.
• Can be excitatory or inhibitory:
- Excitatory: likely to elicit action potential:
Deporalization
-Inhibitory: less likely to elicit action potential:
Hypoerpolarization
Membrane Stabilization

• Depolarize postsynaptic cell
-Brings membrane potential closer to Threshold by opening or closing ion channels.
• Channels affected are:
- Open Na channels
- Close K channels
- Open channels that are equally permeable to Na and
K
Causes depolarization because of the stronger force of Na to flow into the cell
• Depolarization = EPSP (excitatory postsynaptic potential)

Fast EPSPs

Slow EPSPs

EPSPs are Graded Potentials
• Higher freq of APs (presynaptic)
• More neurotransmitter released (presynaptic)
• More neurotransmitter binds to receptors to open
(or close) channels
• Greater increase (or decrease) ion permeability
• Greater (or lesser) ion flux
• Greater depolarization

• Neurotransmitter binds to receptor.
• Channels for either K or Cl open  hyperpolarizes the cell.
• If K channels open, then…
 K moves out  IPSP
(inhibitory postsynaptic potential)
• If Cl channels open, then either…
 Cl moves in  IPSP
 Cl stabilizes membrane potential.

Fast Inhibitory
Synapses Involving
K Channels

• Higher freq of APs (presynaptic)
• More neurotransmitter released (presynaptic)
• More neurotransmitter binds to receptors to open (or close) channels
• Greater increase (or decrease) ion permeability
• Greater (or lesser) ion flux
• Greater depolarization

• 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

Convergence of Input as a Factor in
Summation

Temporal Summation from the same
Synapse

Spatial Summation from Different
Synapses

• Acetylcholine
• Biogenic Amines
• Amino Acid Neurotransmitters
• Neuropeptides
• Autonomic Nervous Sysntem

• Found in the CNS and PNS
• Most abundant neurotransmitter in PNS.
• Synthesis
- Acetyl CoA + choline  acetylcholine +CoA
- Synthesized in cytoplasm of axon terminal
- Biosynthetic enzyme: choline acetyltransferase (CAT)
• Breakdown
- Acetylcholine  acetate + choline
- Degradation occurs in synaptic cleft
- Degradative enzyme: acetylcholinesterase (AchE)

Cholinergic
Synapse

• Nicotinic
- Ionotropic
- Found mostly in the skeletal muscle
- Some found in the CNS
• Muscarinic
- Metabotropic
- Found mostly in the CNS

Actions at Nicotinic Cholinergic
Receptors

Actions at Muscarinic Cholinergic
Receptors

• Derived from amino acids
• Catecholamines – derived from tyrosine
- Dopamine
- Norepinephrine (noradrenaline)
- Epinephrine (adrenaline)
• Norepineprine and epinephrine bind adrenergic receptors
- Alpha and beta adrenergic receptors
- Slow responses at all adrenergic receptors
• Adrenergic receptors are G-protein-coupled
• Generally linked to second messengers

Dopamine
•
Category: biogenic amine
•
Postsynaptic effect: Excitatory or inhibitory
Fig. 6.11

•
Large diversity of metabotropic dopamine receptors (at least 6).
•
Bound by many antipsychotic drugs
Kandel, 2000

Norepinephrine
•
Category: biogenic amine
•
Formed from dopamine
• also in PNS
– sympathetic NS

•
Effect depends on receptor bound
– α-receptors
α
1
vs . α
2
-receptors (see next slide)
– ß-receptors
Silverthorn 2004

Receptors can be Located Presynaptically too –
This will determine their effect
Presynaptic GABA
B receptor actions
Isaacson, J
Neuophysiolgy,

•
Category: biogenic amine
• synthesized from norepinephrine
•
Effect depends on receptor bound
– α-receptors
– ß-receptors

•
Category: biogenic amine
•
Postsynaptic effect: Excitatory
Fig. 6-12

•
Receptors are all G-protein coupled
•
In brain, affects arousal and attention
•
In periphery affects inflamation, vasodilation.
•
Why do some cold medicines make you sleepy? (good exam question).

Category: Biogenic amines
•
Postsynaptic effect: Excitatory

•
Involved in sleep/wakefulness cycle
•
Most receptors are metabotropic, but one group are ionotropic.
•
Why does turkey make you sleepy?
•
SSRI and depression

•
Amino acid neurotransmitters at excitatory
Synapses: glutamate
•
Amino acid neurotransmitters at inhibitory
Synapses: GABA (gamma-amino butyric acid)

•
Category: small-molecule
•
Glutaminergic neurons
•
Postsynaptic effect: depends
•
Very important in CNS
•
Synthesized from glutamine from glia
Glutamate
Fig. 6.6

•
Ionotropic
–
NMDA
• late EPSP
•
Glycine & Mg 2+ dependent
–
AMPA
• early EPSP
– kainate
• early EPSP
•
Metabotropic
Kandel 2000

•
Category: small-molecule
•
GABAergic neurons
•
Postsynaptic effect:
Inhibitory
•
Made from glucose
Fig. 6.8

•
GABA
A
– Ionotropic
– gates Cl channel
•
GABA
B
– Metabotropic
– gates K + channel
Fig. 6.9

• Short chains of amino acids
• E.G., endogenous opiates
- endorphins – found in the brain, morphine-like
- Vasopressin – Anjtidiuretic hormone
(ADH) – found in the posterior pituitary

• Both branches of the ANS innervate most effector organs
• Primary function – regulate organs to maintain homeostasis
• Parasympathetic and sympathetic activities tend to oppose each other
- Parasympathetic Nervous system – rest
- Sympathetic nervous system – fight or flight response

Neurotransmitters and their Receptors in the ANS