Synapse Structure

Question 1

What is a synapse?

Answer 1

A specialized functional contact zone
(junction) for communication between nerve cells (neuro-neuronal), or between a nerve cell and its effector organ (neuromuscular, neuroepithelial, etc.)

Question 2

Synaptic transmisssion

Answer 2

• Bridged junction or gap junction

* Unbridged junction: presence of synaptic cleft

Question 3

Bridged/Gap Junction:

Answer 3

• Bidrectional

* Can be unidirectional

Question 4

Unbridged junction:

Answer 4

• Unidirectional

presynaptic&raquo_space; postsynaptic

Question 5

Electrical Transmission

Answer 5

• Gap: only 3.5 nm wide
• Apposing cells each contributes a hemi-channel = connexon
• 2 connexons form an ion channel: pore size of 1.5 nm in diam.
• Each connexon: 6 connexins
• Each connexin: 4 membrane-spanning regions
• Connexins undergo conformational changes to open or close the pore

Question 6

Electrical transmission is mediated by ______________.

Answer 6

gap junctions

Question 7

Gap junctions:

Answer 7

• Low-resistance, high-conductance channels bridging the 2 cells
• Current flows through the junction and depolarizes the postsynaptic cell
• Most rapid form of synapse between neurons: virtually no synaptic delay

Question 8

Properties of electrical synapse:

Answer 8

• Speed of transmission: no synaptic delay
• Synchronization of transmission: 2 or more electrically-coupled neurons
• Contributes to stereotypic, all-or-none behavior
• Transmission of developmental and regulatory signals between cells
• No mechanisms for inhibitory actions
• No mechanisms for long-lasting changes in effectiveness (modulation) of synapses

Question 9

____________ is the neurotransmitter of the vagus n. to the heart

Answer 9

Ach

Question 10

___________ is the neurotransmitter of the neuromuscular junction

Answer 10

Ach

Question 11

Chemical Transmission is mediated by:

Answer 11

release and diffusion of neurotransmitters into the synaptic cleft

Question 12

Presynaptic (prejunctional):

Answer 12

• Synaptic vesicles
• Active zones:
(presynaptic dense projections)
• Autoreceptors/receptors

Question 13

Synaptic cleft:

Answer 13

• Typically wider than the extracellular

space; 30-50 nm or more

Question 14

Postsynaptic (end-plate;

postjunctional):

Answer 14

• Receptors

* Postsynaptic density (PSD-95)

Question 15

Morphological Types of CNS Chemical Synapses:

Answer 15

Gray’s type I (Asymmetric)

Gray’s type II (Symmetric)

Question 16

Gray’s Type I (asymmetric):

Answer 16

• Round synaptic vesicles
• Wide synaptic cleft
• Prominent PSDs
• Often associated with excitatory synapses

Question 17

Gray’s Type II (symmetric):

Answer 17

• Flat or pleomorphic vesicles
• Narrow cleft
• Less prominent PSDs
• Often associated with inhibitory synapses

Question 18

Monoaminergic synapses:

Answer 18

• Dense-core vesicles
• Axonal varicosities
• Wide synaptic cleft
• No prominent pre- & post-synaptic densities

Question 19

Peptidergic synapses:

Answer 19

• contain large dense-core vesicles

* Vesicles are of different sizes & shapes

Question 20

Neuromuscular Junction:

Answer 20

• Presynaptic dense bars
• Ca++ channels
• Primary & secondary synaptic clefts
• AChE and basal lamina in clefts
• Postsynaptic junctional folds
• Ach receptors face active zones
• Voltage-gated Na+ channels along sides and depths of folds

Question 21

Myasthenia Gravis:

Answer 21

Disease of chemical transmission at the neuro-muscular synapse
• Severe weakness of muscles
Autoimmune: most common Antibodies against one’s own nicotinic acetylcholine receptors (AChR) in muscles. Congenital and heritable: rare
• Treatment: Inhibitors of acetylcholinesterase

Question 22

What are symptoms of myasthenia gravis?

Answer 22

• Severe weakness of muscles
Autoimmune: most common; antibodies against one’s own nicotinic acetylcholine receptors (AChR) in muscles
Congenital and heritable: rare

Question 23

How is myasthenia gravis treated?

Answer 23

Inhibitors of acetylcholinesterase

Question 24

Tetanus toxin:

Answer 24

cleaves VMAP

Question 25

Botulinum toxins:

Answer 25

cleave VAMP or t-SNARE

Question 26

α-Latrotoxin:

Answer 26

binds to neurexin

Question 27

Synapsin I:

Answer 27

* binds vesicles to cytoskeleton * phosphorylated by Ca2+/calmodulin-dependent protein kinase * when intracellular Ca2+ is increased >> releases vesicles from the cytoskeleton

Question 28

Rab3A:

Answer 28

* a neuron-specific GTPase | * binds to vesicles essential for propelling vesicles to the active zone

Question 29

Synaptotagmin:

Answer 29

* has 5 Ca2+-binding sites | * major Ca2+-sensing protein that triggers vesicular exocytosis

Question 30

NSF:

Answer 30

N-ethylmaleimide-sensitive factor (an ATPase): • cytosolic • hydrolyzes ATP to release the complex

Question 31

v-SNARE (vesicular SNAP Receptor proteins) = VAMP (vesicle-associated membrane protein):

Answer 31

Synaptobrevin: binds t-SNARE

Question 32

t-SNARE (target membrane SNAP Receptor):

Answer 32

Syntaxin: a plasma membrane protein | SNAP-25: a plasma membrane protein of 25 kDa

Question 33

What is the process for v-SNARE & t-SNARE associate proteins?

Answer 33

v-SNARE & t-SNARE associate >> docking & fusion >> NSF & SNAP bind to complex & dissociate it

Question 34

Neurexin:

Answer 34

plasma membrane protein | may also interact with vesicle proteins

Question 35

SNAP:

Answer 35

* soluble NSF attachment protein * unrelated to SNAP-25 * cytosolic * binds to NSF

Question 36

Postsynaptic Receptors:

Answer 36

determine postsynaptic response

Question 37

Common biochemical features:

Answer 37

Common biochemical features: Membrane-spanning proteins with external recognition sites for specific transmitter molecules. Effector function triggered in target cell: • Directly activates gating of ion channel -or- • Indirectly activates gating through second messenger cascade • A given transmitter binds to conserved families of receptors and is associated with specific physiological functions