Synapses and Neurotransmission

Question 1

What part of a neuron is an action potential generated on?

Answer 1

Axon Hillock (it has a lowered threshold than normal resting membrane so APs are readily triggered in this region)

Question 2

Are the graded potentials under Schwann cell myelination above or below threshold?

Answer 2

Above (if they fall below threshold, ‘propagation’ to adjacent Nodes of Ranvier is not possible)

Question 3

Why don’t graded potentials under Schwann cells result in Action potential generation?

Answer 3

Sodium and potassium channels are inactivated, or even missing sometimes in these areas

Question 4

What is the space constant?

Answer 4

distance at which graded potential has decreased by 63% = space constantA large space constant means that there is a long distance before signal decays by 63% (good thing).

Question 5

What is it called when an axon synapses to an axon?

Answer 5

axoaxonic synapse

Question 6

What is an orthodromic neuron?

Answer 6

APs are conducted the normal way- from the soma down the axon

Question 7

What is an antidromic neuron?

Answer 7

APs are conducted from an axon to the soma (keep in mind that this is the opposite route for conventional signal transduction- i.e. orthodromic)

Question 8

Name two excitatory neurotransmitters

Answer 8

acetylcholine and glutamine

Question 9

Name two inhibitory neurotransmitters

Answer 9

GABA and glycine

Question 10

Name two modulatory neurotransmitters

Answer 10

dopamine and serotonin

Question 11

Are the tunnels in synaptic clefts through which electrical signals are conducted sodium or potassium channels?

Answer 11

neither (remember, we are talking electrical signaling here- not chemical)

Question 12

What are the common distinctions between chemical and electrical signals?

Answer 12

1. Electrical - i.e. heart cellsa. electrical contactb. minimum synaptic delayc. bidirectionald. allows for synchronous activation2. Chemical - i.e. neuromuscular junction a. chemicalb. 0.5-1.0 msec delay at the synapsec. unidirectional

Question 13

What are the basic steps of a neuromuscular junction?

Answer 13

􏰂presynaptic is nerve, postsynaptic is muscle􏰂 1) when nerve is activated the synaptic vesicles will fuse with the presynaptic membrane and release acetylcholine into the synaptic cleft 􏰂 2) postsynaptic membrane (end plate of a muscle) binds acetylcholine at ligand gated receptors, a channel opens, and this triggers an end plate potential (EPP)3) 􏰂 acetylcholinesterase in the synaptic cleft breaks down acetylcholine to acetic acid and choline􏰂NOTE: EPP is not an AP but a graded depolarization at the muscle end plate

Question 14

What is always the neurotransmitter at a neuromuscular junction?

Answer 14

acetylcholine

Question 15

NMJ- Once the postsynaptic membrane (end plate of a muscle) binds acetylcholine at ligand gated receptors, a channel opens, and this triggers what?

Answer 15

an end plate potential (EPP). No voltage dependent Na+ channels are in the end plate so only graded depolarizations occur in the form of EPP and not an AP

Question 16

Is an end plate potential (EPP) an AP or graded depolarization?

Answer 16

graded depolarization

Question 17

What enzyme breaks down acetylcholine from the postsynaptic membrane and what are the products of this reaction?

Answer 17

Acetylcholinesterase; acetic acid and choline (choline is retaken backup into the presyn terminal to synthesize new acetylcholine)

Question 18

What are the events associated with presynaptic movement of neurotransmitter into the synaptic cleft?

Answer 18

1) Action potential travels down axon to presynaptic terminal2) Membrane depolarization opens voltage dependent Ca2+ channels, allowing Ca2+ to rush in.3) Ca2+ influx activates protein kinase which phosphorylates synapsin l4) Phosphorylation of synapsin l promotes binding of synaptic vesicles to inside membrane of presynaptic terminal.5) Ach released into synaptic cleft6) Ach diffusion to postsynaptic membrane

Question 19

An Ach receptor at the neuromuscular junction is more specifically call a what?

Answer 19

nicotinic receptor

Question 20

What are the events associated with neuromuscular joints after Ach has released into the synaptic cleft?

Answer 20

1) Ach molecules bind to Ach receptor on postsynaptic membrane2) Ach binding causes gate to open in channel (i.e. ligand activating channel) , allowing K+ and Na to flow down their concentration gradients, leading to depolarization (NOTE: this channel is a non-specific Na and K, ligand activated channel - don’t confuse this with voltage gated Na channels or voltage gated K channels or Na/K ATPase pump)3) depolarization due to more Na influx over K efflux (end plate potential) leads to opening of voltage-dependent Na+channels, membrane. Threshold is reached resulting in an action potential (an AP in muscle leads to muscle contraction)

Question 21

Note on Quantal Release of Ach

Answer 21

1) each acetylcholine vesicle contains the same amount of acetylcholine2) fusion of one synaptic vesicle is not enough to get above threshold3) fusion of one vesicle generates a miniature end plate potential (MEPP)4) increasing the amount of acetylcholine in cleft results in an increase in height of end plate potential.5) increase the EPP and you increase the probability of an action potential occurringNOTE: MEPPs occur constantly in healthy individuals. MEPPs are absent in certain diseases OR hyperactive such that a single (or very few) synapses can generate MEPPs

Question 22

What do Ach agonists and antagonists do?

Answer 22

Antagonist - binds to receptor and inhibits the normalresponse of the receptor, inhibiting an EPPAgonist - binds to receptor and activates the normal response of the receptor, generating and EPP

Question 23

What does Curare (cure-are-ee) do to in relation to EEP?

Answer 23

Curare is an Ach antagonist. It binds to Ach binding site but doesn’t activate channels, blocks Ach from binding, decreases EPP and activation of muscle, i.e. diaphragm and asphyxiation

Question 24

What does Neostigimine (drug) do in relation to EEP?

Answer 24

increases Ach in synaptic cleft by inactivating acetylcholinesterase, increases EPP

Question 25

What does Myasthenia Gravis (disease) do in relation to EEP?

Answer 25

autoimmune disease causing destruction of Ach receptors causing decreased EEP

Question 26

What does Hypocalcemia do in relation to EEP?

Answer 26

Two contradictory effects: (1) decreased Ca into presynaptic terminal, decreased neurotransmitter release, decreased EPP, causing decreased frequency of AP, and(2) decreased Ca binding to Na channels resulting in hyperexcitable Na channels, increasing frequency of AP (rickets). MAIN effect = hyperexcitable Na channels and increased AP frequency.

Question 27

What does Botox do?

Answer 27

prevents synaptic vesicles from fusing and releasing acetylcholineClinical Application: decrease muscle activity of overly active muscles, for example ‘uncontrollable blinking’ (blepharospasm).History: In its use for eye muscle disorders, it was observed Botox softened frown lines.

Question 28

How do Inhibitory Post Synaptic Potentials (IPSPs) work?

Answer 28

Opening a K+ channel leads to net efflux of K and hyperpolarization (remember there is no change in concentration) IPSP – farther from thresholdNeurotransmitter can have different end effects based on the channel it opens. Channel that opens determines if IPSP or EPSP. In the heart, Ach creates an IPSP via K channel.

Question 29

What are Temporal and Spatial Summation?

Answer 29

1) Temporal- In temporal summation, 1 presynaptic nerve is being stimulated rapidly leading to a summation of EPSP. If the sum of EPSPs is above threshold, then an action potential is generated2) Spatial- In spatial summation, 2 presynaptic nerves are being stimulated spatially near each other at the same time. If presynaptic neurons A and B are both fired rapidly and their effects sum to reach threshold, an AP is generated. NOTE: There is a temporal component to spatial summation- If there is too much time between stimulation of nerve A and nerve B, they will not summateeffect of location: B nerve elicits greater depolarization than A since B is closer to the axon hillock (and recording device) on postsyn nerve

Question 30

What are the steps of IPSP Summation

Answer 30

Example:1) presynaptic nerve C is stimulated, causing hyperpolarization or IPSP on postsynaptic nerve2) If nerve C is stimulated twice very quickly in time = temporal summation results and a larger IPSP is generated (i.e farther from threshold meaning that it is unlikely that an AP will occur)3) spatial summation of IPSPs occurs when two inhibitory presynaptic nerves fire at near the same time. Some nerves have many synapses, activation / inactivation of postsyn nerve depends on the summation of many EPSPs and IPSPs

Question 31

Motor neurons are under constant inhibition and activation via IPSPs and EPSPs, a checks and balances system. What happens if you remove IPSPs via Strychnine?

Answer 31

-strychnine is a glycine antagonist-glycine is typically involved in IPSPsIf you antagonize glycine, the number of IPSPs decreases. When a signaling pathway is activated only with EPSP, the result is cramping of the diaphragm and death

Question 32

What does valium do?

Answer 32

Valium enhances GABA’s ability to cause IPSPs so the number and duration of IPSPs increases resulting in a feeling of relaxation

Question 33

Cholinergic synapses use which neurotransmitter?

Answer 33

Acetylcholine

Question 34

Nicotinic receptors are activated by which neurotransmitters?

Answer 34

activated by acetylcholine and nicotine (example: at a neuromuscular junction)Note: these are a type of ‘cholinergic’ synapse

Question 35

Muscarinic receptors are activated by which neurotransmitters?

Answer 35

activated by acetylcholine and muscarineNote: these are a type of ‘cholinergic’ synapse

Question 36

Dopaminergic and Adrenergic synpases use neurotransmitters of which class?

Answer 36

Catecholamines (i.e. norepinephrine, epinephrine, and dopamine)

Question 37

Adrenergic synapses use which neurotransmitter?

Answer 37

norepinephrine = noradrenalineor epinephrine = adrenaline

Question 38

Dopaminergic synapses use which neurotransmitter?

Answer 38

dopamine

Question 39

Amino Acid synapses use which neurotransmitters?

Answer 39

GABA (gamma amino-butyric acid) and glycine= usually IPSPglutamate and aspartate = usually EPSP

Question 40

How does dopamine function in relation to Parkinson’s disease and schizophrenia?

Answer 40

Dopamine is a common neurotransmitter of the midbrain-binds to D1 and D2 receptors a decrease in D2 receptors is seen in Parkinson’s an increase in D2 receptors is seen in schizophrenia

Question 41

What does glutamate bind to?

Answer 41

• most common excitatory neurotransmitter in brain- binds to kainate receptor

Question 42

What is a neuromodulator?

Answer 42

substance that modifies neurotransmitter release (presynaptic) or action (postsynaptic)

Question 43

How do neuromodulators work?

Answer 43

1.) mechanism of action is usually through a 2nd messenger 2.) usually has a prolonged effect (examples: change # of postsynaptic receptors orcause long-term changes in channel conductances presynaptically)3.) release site distant from synapse and receptor4.) Funtional observation - MODIFIES magnitude of postsyn potential/duration of postsyn potentialExample: steroids decrease the number of GABA receptors in brain, resulting in fewer IPSPs and a change in behavior related to violence

Question 44

Where are electrical synapses common?

Answer 44

heart

Question 45

What is the value of physically connecting the pre- and post- synaptic neurons in electrical synapses?

Answer 45

there is minimal synaptic delay, thus increasing the speed of the AP and the propagation of an AP can be bidirectional (whereas, chemical synapses are unidirectional)