Synapses; NT Release; Metabotropic Receptors; Synaptic Modulation: Module 2.3-2.5

Question 1

What are the 2 types of synapses?

Answer 1

• Electrical
• Chemical

Question 2

What is characteristic of an electrical synapse image?

Answer 2

Membranes touching leaves no space for vesicles.

Question 3

What are the distinctions between electrical and chemical synpases?

Answer 3

Distance Between Membranes
- Electrical Synapses: 3nm
- Chemical Synapses: 30nm(neuronal) - 50nm(nerve-muscle)

Time is the main Difference Metabotropic: Coupling Mechanism Ionotropic: Ion Channels

Question 4

What channels generate the current in the post synaptic cell in synaptic transmission at an electrical synapse?

Answer 4

Voltage Gated Ion channels in the Presynaptic Cell.

Question 5

Is Electrical Transmission Graded?

Answer 5

Yes. It occurs even when the current in the presynaptic cell is below the threshold for an action potential.

Reduction in Amplitude in Post synaptic to do more distance travelled.

Question 6

Where was the first electrical synapse found?

Answer 6

Crayfish Giant Motor Synapse

Question 7

What are the functions Gap junctions?

Answer 7

• Connect Two Cells wiht a large and unselective pore (Allows everything to pass)
• They allow the passage of ions small molecules as large as 1kDa
• They provide pathways for both chemical and electrical communication

In Chemical - They allow NT precursors to be transferred between neurons

Question 8

Explain the Gap Junction Structure.

Answer 8

• Two apposed hexameric structures called connexons, one contributed by each cell.
• Connexons contact eachother to bridge a gap of 3nm between membranes.
• Connexon has six identical subunit surrounding a central pore - radial hexameric symmetry.
• Each subunit is called a connexin(Cx) - Molecular of 26-46 kDa.
• Diameter of Pore has diameter of 1.2 - 2nm
• Cytoplasmic end of connexon - funnel shaped entrance.

Question 9

What are reciprocal synapses?

Answer 9

Gap Junctions that pass electrical current in both directions with equal frequency.

Question 10

What is the current type(IV plot relation) passing through the gap junction?

Answer 10

Ohmic

Voltage = Voltage Diff between cells

Question 11

How do gap junctions arrange at the membrane?

Answer 11

Forms Plates with very little membranes left.

Connexons can shut off through a rotation mechanism.

Question 12

Explain the mechanism of Gap Junction(Connexon) gating.

Answer 12

Increases in [Ca2+]i can cause gap junctions to close.

In the absence of Ca2+, the pore is in an open configuration and the
connexin subunits are tilted 7 - 8 degrees from an axis perpendicular to
the plane of the membrane. After the addition of Ca2+, the pore closes
and the subunits move to a more parallel alignment. The gating of the
gap junction channel may thus correspond to a conformational change
that involves concerted tilting of the six connexin subunits to widen
(open) or to constrict (close) the pore.

Closure Used to Prevent Apoptosis of Next Cell

Question 13

Are Connexin Subunits diverse?

Answer 13

Yes

Every Tissue(Smooth Muscle. Epithelia) can have gap junctions.

Different types of Connexins in Each one

Question 14

What are the 4 different type of gap junctions?

Answer 14

Homo/Hetero meric - For a given connexon hexamer - Same or Different Connexins

Homo/Hetero Typic - Apposition of idential or different connexon hexamer.

1. And HomoMeric 2. And Heteromeric 3. And HomoMeric 4. And HeteroMeric

Question 15

What are connexin hemichannels?

Answer 15

Connexin hemichannels are half of a gap junction channel. Each hemichannel, or connexon, is a hexameric assembly of six protein subunits called connexins. These hemichannels are embedded in the plasma membrane of a cell and serve as a conduit between the intracellular and extracellular environments.

Involved in Pathological Conditions

Question 16

Describe the synapse of the neuromuscular junction.

Answer 16

The axon of the motor neuron
innervating the muscle ramifies into
several branches. Each branch forms
synaptic boutons (swellings). The
boutons lie over a specialized region of
the muscle membrane, the end-plate,
and are separated from the muscle
membrane by a 100-nm synaptic cleft.
Synaptic vesicles clustered around
active zones, where the
neurotransmitter acetylcholine (ACh) is
released. Immediately under each
bouton in the end-plate are several
junctional folds, the crests of which
contain a high density of ACh
receptors.

Question 17

What are synaptic boutons and dendritic spines?

Answer 17

• Synaptic boutons are small swellings that are found at the terminal ends of axons. Synaptic boutons are the sites where synapses are
  found and is where neurotransmitters are stored in vesicles.
• Dendritic spines are protrusion from a neuron’s dendrite thatreceives a synaptic input from an axon. It is the side of the synapse where neurotransmitter receptors are located.

Question 18

Dendritic Spines are Highly Dynamic

Variable ____ and volume correlates with the ____ of each spine synapse.

Answer 18

Variable spine shape and volume correlates with the strength and maturity (size of EPSP) of each synapse.

Question 19

What shape of dentritic spine has stronger response?

Answer 19

Shapes with more volume.

Question 20

What are the different types of dentritic shapes?

Answer 20

Note one denrite can have many spines with many different shapes

Most Receptors are Type V - Best shape to trap NT Type of Spine is dependant on the connection.

Question 21

How many vesicles and NT are in typical presynaptic chemical synapses?

Answer 21

Typically contain 100 to 200 synaptic vesicles each of which contain several thousand NT.

Question 22

What does amplification in chemical synapses refer to?

Answer 22

Chemical transmission lacks the speed of electrical synapses, but it amplifies signals: one synaptic vesicle releases several thousand of transmitter that together can open thousands of ion channels in the target cell.

Question 23

Describe the process of synaptic transmission at chemcial synapses.

Answer 23

Question 24

What are the two types of post synaptic receptors?

Answer 24

Question 25

What are the two biochemical features that all receptors for chemical transmission have?

Answer 25

1. They are membrane-spanning proteins that recognize and binds the transmitter. 2. They carry out an effector function within the target cell

Question 26

Who discovered quantal release of neurotransmitter?

Answer 26

Fatt, Euler, Axelrod, | Novel Prize in 1970

Question 27

What are miniature end-plate potentials?

Answer 27

Electrophysiological "noise" - Tiny Depolariztions = 0.4mV ## Footnote Size of these suggested that they occur in discrete multiples of unitary amplitude

Question 28

What is an inhibitor for AchE?

Answer 28

Neostigmine.

Question 29

Is Ach release quantized?

Answer 29

Yes, MEPPs led to this finding, quantum event corresponds to ACh release from one synaptic vesicle. | Miniature end-plate potentials

Question 30

What factor does amplitudes of end plate potentials increase by?

Answer 30

0.4 mV | Corresponds with 1 more vesicle being released each time.

Question 31

What is the equation that describes the mean number of **quanta** releasd after a single impulse?

Answer 31

Question 32

Where does the main delay of chemical transmission come from?

Answer 32

Delay of Ca Influx | Need accumulatin of Ca in the Presynaptic to cuause release of vesicles.

Question 33

What is Amperometry?

Answer 33

**Presynaptic detection** of **neurotransmitter release** by **carbon fiber electrode**.

Question 34

Explain Capacitance measurements as an indicator exo/endocytosis and NT release.

Answer 34

Release of vesicles increase membrane area which increases capacitance that we can measure to quantify release of NT.

Question 35

What is the sniffer patch technique?

Answer 35

**Outside Out Membrane Patch** expressing a high density of the dsired receptors. **Voltage Clamped** Another electrode stimulated neuron of interest, releaseing NT on the detector patch.

Question 36

What technique of measuring is used to determine what NT is released?

Answer 36

Sniffer Patch Technique

Question 37

What type of curve/relationship does presynaptic Ca have on transmitter release?

Answer 37

**Sigmoid shape** on a logarithmic scale. Eventually has a **max**. (Limited # of Vesicles)

Question 38

Explain the structure of how vesicles are attached to the membrane.

Answer 38

Question 39

What Protein does Ca bind to for vesicle release?

Answer 39

Synaptotagmin

Question 40

Explain how Ca binds to Synaptotagmin.

Answer 40

**Is an integral vesicle membrane protein that act as Ca Sensors. Needs to bind 5 Ca to activate. C2A Subunit Binds 3, C2B Binds 2.** The short N-terminal tail (the vesicle lumen), is followed by a single hydrophobic domainm(vesicle membrane) and a long cytoplasmic tail that contains two C2 domains (C2A and C2B) near the C terminus. The C2 domains are calcium- and phospholipid-binding motifs.

Question 41

Explain the zippering process of the synaptotagmin-complexin-SNARE complex.

Answer 41

Question 42

Describe the SNARE complex structure?

Answer 42

Consists of a bundle of four a-helixes, one each from synaptobrevin and syntaxin and two from SNAP-25.

Question 43

What are the steps of the formation and dissociation of the SNARE Complex?

Answer 43

1. Synaptobrevin interacts with two plasma membrane target proteins, the transmembrane protein syntaxin and the peripheral membrane protein SNAP-25. 2. The three proteins form a tight complex bringing the vesicle and presynaptic membranes in close apposition (see part B). Munc18 binds to the SNARE complex. 3. Calcium influx triggers rapid fusion of the vesicle and plasma membranes; the SNARE complex now resides in the plasma membrane. 4. Two proteins, NSF and SNAP (unrelated to SNAP-25), bind to the SNARE complex and cause it to dissociate in an ATP-dependent reaction

Question 44

What is the active zone?

Answer 44

The **active zone** is a **specialized region** of the **presynaptic neuron** at the synapse where neurotransmitter release occurs. It is a **highly organized structure** located within the presynaptic membrane, facing the synaptic cleft and directly opposite the postsynaptic density. This zone is **crucial for efficient synaptic transmission**.

Question 45

What are the three filamentous structures of the active zone and how are they organized?

Answer 45

1. Pegs 2. Beams 3. Ribs

Question 46

Where are the Cav channels in relation to the active zone machinery?

Answer 46

Structure over area of membrane with **Cav channels lined up with the pegs and ribs**.

Question 47

What does a G-coupled receptor (GPCR) have the ability to do?

Answer 47

Have the ability to bind and **hydrolyze guanosine triphosphate (GTP) to GDP**.

Question 48

Do transmitters one have one type of receptor they act on?

Answer 48

No, many transmitters have both types of receptors that they act on.

Question 49

Explain the G protein activation cycle.

Answer 49

Question 50

What is the function of AC (Adenylyl Cyclase) and what activates and inhibits it?

Answer 50

**Converts ATP to cAMP**, which when then activate protein Kinase A. Activated by Alpha stimulatory subunits from g-proteins. Inhibited by Alpha inhibitory subunits from g-proteins.

Question 51

What is phototransduction and what is the G-protein mechanism?

Answer 51

**Phototransduction** is the biological process in which **light is converted into electrical signals** in cells. | Mechanism:

Question 52

How does G-proteins act via phospholipase?

Answer 52

Question 53

What are the two levels of amplification in chemical synapses?

Answer 53

1. Presynaptic: Neurotransmitter release 2. Metabotropic Receptors: Signalling Pathways | Metabotropic Amplification Example

Question 54

Can one neurotransmitter have a variety of divergent effects?

Answer 54

Yes, can activate multiple receptors stimulating different pathways. Can affect different neurons or different parts of a neuron differently depending on receptor types expressed.

Question 55

What does it mean when it says neurotransmitters can have convergent effects?

Answer 55

**Multiple transmitters**, each activating its **own receptor type**, **converge on a singe type of ion channel** in a single cell and stimulate the **same effect**.

Question 56

What is an example of a convergent effect in pyramidal cells of the hippocampus?

Answer 56

**GABA, 5-HT1A, A1** (adenosine), and **SS** (somatostatin) receptors, all of which activate the same K+ channel. **NE, ACh, 5-HT, corticotropin-releasing hormone, and histamine** all converge on and depress the slow Ca2+- activated K+ channels.

Question 57

# Given that brain modulatory systems differ in structure and funtion: What are the 4 similarities of all brain modulatory systems?

Answer 57

1. **Small set of Neurons** (several thousand) **forms the center of the system**. 2. The neurons of the system **arise from the central core of the brain**; mostly from the **brainstem**. 3. **Each neuron influences many others**; has an axon that contacts more than 100,000 postsynaptic neurons across the brain. 4. The **synapses are designed to release transmitters widespread into ECF** to act on mny neurons instead of a single synaptic cleft. | IPSP and EPSP are all done through ionotropic receptors.

Question 58

Where do all synaptic modulatory systems originate from and what are some examples of these systems?

Answer 58

The brainstem.

Question 59

What synpatic modulatory pathway is indicated by the image below and how does it work?

Answer 59

The Norepinphrine System (Locus Coeruleus) **Axons arising from the locus coeruleus synapse** on pyramidal cells in the cerebral cortex, where they **release NE**. **NE acts on β-adrenergic receptors in the pyramidal cell** membrane. **NE inhibits** multiple **K currents**. The effect of NE by itself has **little or no influence on the activity of a resting neuron**. However, **a cell exposed to NE will react more powerfully when it is stimulated** by a strong excitatory input (usually glutamatergic). **Thus, NE modulates the cell’s response to other inputs.**

Question 60

What is the NE system involved in?

Answer 60

* Regulation of Attention * Arousal * Sleep-Wake Cycle * Learning * Memory * Anxiety * Pain * Mood * Brain Metabolism

Question 61

What effect does NE have on pyramidal cells?

Answer 61

**Increases Neuronal excitability** in pyramidal neurons via **B-Andregenic Receptors** and **PKA**. | Tunes up response of Cells

Question 62

What are the 2 cellular sites at which modulation by second messengers can occur?

Answer 62

**Presynaptic**: Second Messengers can **regulate efficacy and duration of transmitter release** in turn effecting the size of the PSP. Example: Altering Ca influx by directly modulating Cav channels or indirectly modulatng K channels which alters Ca influx. **Postsynaptic**: Second Messengers can elter directly the **amplitdue of the PSP** by **modualting ionotropic receptors**.