ICL 3.1: Synaptic Transmission

Question 1

how do neurons communicate with each other and other peripheral structures?

Answer 1

through the generation of chemical and electricalsignals

Question 2

what is a synapse?

Answer 2

the junction point from one neuron to the next

Question 3

what are the two types of synapses?

Answer 3

1. chemical
2. electrical

these can be either excitatory or inhibitory

Question 4

how do electrical synapses work?

Answer 4

gap junction proteins (connexons) aggregate to form an aqueous channel

action potentials are then transmitted through gap junctions –> no synaptic vesicles of significant synaptic cleft

the molecules passing through could be ions like Ca+2 or other small molecules like ATP

signal transmission is bidirectional

electrical synapses are the fasts way neurons communicate with one another!

Question 5

how do chemical synapses work?

Answer 5

this type of synapse is the most abundant in the human CNS

the way it works is that the presynaptic neuron secretes a neurotransmitter which then binds to receptor proteins in the membrane of the postsynaptic neuron

the NTs will either modulate, stimulate or inhibit the postsynaptic neuron

signal transmission is unidirectional

Question 6

what are the basic components of a chemical synapse?

Answer 6

1. synaptic cleft
2. transmitter vesicles
3. post synaptic neuronal membrane
4. mitochondria

Question 7

what is the synaptic cleft?

Answer 7

it separates the presynaptic terminal from the postsynaptic neuron

Question 8

what is the function of the presynaptic terminal?

Answer 8

the terminal hastransmitter vesicles and themitochondria

transmitter vesicles contain neurotrans­mitters

Question 9

what is the function of the postsynaptic neuronal membrane?

Answer 9

it containsexcitatory or inhibitory receptors

Question 10

what is the function of mitochondria in a chemical synapse?

Answer 10

mitochondria provide ATP to use as an energy source for neurotransmitter synthesis

Question 11

what are the events that happen at a chemical synapse?

Answer 11

1. an action potential depolarizes the presynaptic membrane
2. voltage gated Ca2+ channels on the presynaptic membraneopen and a large number of Ca2+ ions enter the presynaptic terminal
3. Ca2+ entry leads to the exocytosis of synaptic vesicle contents
4. NTs are released into the synaptic cleft
5. NTs bind to receptors on post synaptic membrane
6. brief opening of specific ion channels
7. NTs are soon released and degraded or recycled

Question 12

how much neurotransmitters are released at a chemical synapse?

Answer 12

Quantity of neurotransmitter released is directly related to the number of Ca2+ ions that enter the presynaptic neuron

Question 13

after an event at a chemical synapse, how is the synaptic cleft cleared?

Answer 13

1. Its can be returned to axon tmerinals for reuse or transported into glial cells
2. enzymes can inactivate NTs
3. NTs can diffuse out of the synaptic clef

Question 14

what breaks down acetylcholine?

Answer 14

acetylcholinesterase

ACh is made from choline and acetyl CoA –> in the synaptic cleft, ACh is broken down by acetylcholinesterase and the choline is transported back into the axon terminal and used to make more ACh

Question 15

how do synaptic vesicles in the presynaptic neuron exocytose their NTs into the synaptic cleft?

Answer 15

the synaptic vesicles dock at defined sites on the target plasma membrane –> the SNARE family of proteins is what mediates the docking of the transport vesicles with the target membrane

Ca2+ influx triggers the fusion leading to the opening of the pore

once the vesicles fuse with the membrane, NTs are related into the synaptic clef

Question 16

what is the MOA of botulism?

Answer 16

Botulinum neurotoxins are synthesized primarily by different strains of the anaerobic bacteriaClostridium botulinum

botulinum toxin, or botox, is used in the therapeutic setting to reduce muscle tension, toreduce muscle spasticity

the botox injection work by weakening or paralyzing certain muscles or by blocking certain nerves

they do this by cleaving SNARE complex proteins which prevents the fusion of vesicles to the plasma membranes

Question 17

what are the 2 major classes of neurotransmitters?

Answer 17

1. small molecule transmitters

ionotropic receptors and metabotropic receptors

2. peptide transmitters

metabotropic receptors

Question 18

what are small molecule transmitters?

Answer 18

they’re the most acute and rapid responses

they’re used for the transmission of sensory signals to the brain and of motor signals back to the muscles

class I-IV: examples include ACh, epinephrine, serotonin, histamine, glycine, nitric oxide etc.

Question 19

where are small molecule transmitters synthesized?

Answer 19

they’re synthesized in the cytosol of the presynaptic terminal and absorbed by active transport into transmitter vesicles

Question 20

what are the 8 important small molecule neurotransmitters?

Answer 20

1. acetylcholine
2. norepinephrine
3. dopamine
4. serotonin
5. glutamate
6. nitric oxide
7. glycine
8. GABA

Question 21

what is the function of acetylcholine?

Answer 21

a small molecule neurotransmitter

it’s a majorexcitatory neurotransmitter of somatic motor neurons

it has some inhibitor effects like the inhibition of the heart by the vagus nerves

it also has a modulatory role in cognitive functions like paying attention

Question 22

what is the function of norepinephrine?

Answer 22

a small molecule neurotransmitter

it’s mostly excitatory and is secreted in the brain stem and hypothalamus

it controls overall activity and mood of the mind – so your sense of feeling good or being alert

it also increases heart rate and BP

Question 23

what is the function of dopamine?

Answer 23

a small molecule neurotransmitter
it’s released from the brain and it mediates various aspects of cognition

so it facilitates your sense of feeling good and your reward pathway

in Parkinson’s, there’s a loss of dopamine neurons in the midbrain-substantial nigra

Question 24

what is Parkinson’s MOA?

Answer 24

in Parkinson’s, there’s a loss of dopamine neurons in the midbrain-substantial nigra

as the substantia nigra degenerates in Parkinson’s disease, the nigrostriatal pathway is disrupted, reducing striatal dopamine and producing PD symptoms

Question 25

what is the function of serotonin?

Answer 25

a small molecule neurotransmitter that's released from the brain and it mediates various aspects of cognition it's an inhibitor of pain pathways in the spinal card it also regulates endocrine activity aka hormonal controls! its also involved in the mood of a person and controls sleep/wake cycles; it causes sleepiness

Question 26

what happens if someone has inadequate serotonin levels?

Answer 26

1. severe depression 2. obsessive/compulsive disorders 3. anger issues 4. eating disorders

Question 27

what is the function of glutamate?

Answer 27

a small molecule neurotransmitter that is secretes and concentrated in the brain it's the major excitatory neurotransmitter in the CNS

Question 28

what is the function of nitric oxide?

Answer 28

a small molecule neurotransmitter that's secreted by nerve terminals in areas of the brain responsible for long-term behavior and memory it's synthesized instantly as needed and diffuses out of the presynaptic terminals and then into postsynaptic neurons it changes intracellular metabolic functions that modify neuronal excitability in the postsynaptic neuron

Question 29

what is the function of glycine?

Answer 29

a small molecule neurotransmitter that is secreted mainly in the spinal cord it is inhibitory* it's also a co-transmitter for some glutamate receptor (binding is important for the activity)

Question 30

what is GABA?

Answer 30

a small molecule neurotransmitter secreted in the spinal cord and CNS it's the most important inhibitory transmitter int he brain!!! it's what inhibits NTs that cause anxiety

Question 31

what are benzodiazepines? give examples

Answer 31

benzodiazepines are tranquilizers that are used for anxiety and insomnia they work with GABA to limit anxiety ex. valium (diazepam) and xanax (alprazolam)

Question 32

what are peptide transmitters?

Answer 32

neuropeptides have slower but longer lasting effects (days, months or years) they're present in smaller quantities but are more potent

Question 33

where are peptide transmitters synthesized?

Answer 33

they're synthesized by ribosomes in the neuronal cell body they undergo packaging in the ER and subsequently the golgi then, vesicles are transported to the tips of the nerve fibers by axonal streaming  (slow process)

Question 34

what are the two types of receptor proteins of a synapse?

Answer 34

the membrane of the postsynaptic neuron contains a large numbers of receptor proteins 1. ionotropic receptors 2. metabotropic receptors each receptor has an extracellular components that protrudes into the synaptic cleft and binds the neurotransmitter there's also an intracellular component extending into the interior of the postsynaptic neuron

Question 35

what are ionotropic receptors?

Answer 35

a type of receptor in a synapse that gates ion channels directly and allows for passage of specific ions so they're membrane-bound receptor proteins that respond to ligand binding by opening an ion channel and allowing ions to flow into the cell, either increasing or decreasing the likelihood that an action potential will fire there are both cation channels and anion channels they're fast and precise

Question 36

what are metabotropic receptors?

Answer 36

a type of receptor in a synapse that activates "second messengers" so there are molecules that activate other substances inside the cytoplasm of the postsynaptic neuron prolonged postsynaptic neuronal excitation or inhibition (such as memory) is achieved by activating a “second messenger” chemical system inside the postsynaptic neuronal cell ex. G proteins

Question 37

what are cation channels?

Answer 37

usually for Na+ ions but can also be for K+ or Ca+2 the channels are lined with negative charges to attract positively charged Na+ ions --> negative charges repel Cl- ions and other anions & prevent their passage ions will enter when the channel diameter > size of the hydrated Na+ ion

Question 38

what are anion channels?

Answer 38

they mainly allow Cl- ions to pass but also minute quantities of other anions Na+, K+ and Ca2+ ions are blocked because of the size of their hydrated ions

Question 39

how do G proteins work?

Answer 39

they're a type of metabotropic receptor system the inactive G protein complex is free in the cytosol but it undergoes a conformation change when a receptor is activated by a neurotransmitter this leads to a series of cellular events via secondary messengers including the opening of ion channels

Question 40

what different things can secondary messengers in a metabotropic receptor system do?

Answer 40

1. opening specific ion channels -- often stays open for a prolonged time unlike ion channels 2. activation fo cAMP or cGMP which then in turn activate highly specific neuronal metabolic machinery and initiate any one of many chemical results 3. activation of one or more intracellular enzymes -- the enzymes in turn can cause any one of many specific chemical functions 4. activation of gene transcription -- this can lead to formation of new proteins which in turn changes nruronal metabolic machinery or structure

Question 41

what's the resting membrane potential of a spinal motor neuron?

Answer 41

the soma of a spinal motor neuron has a resting membrane potential of ~ − 65 mV synaptic potentials arise when neurotransmitters activate ion channels

Question 42

what 2 synaptic potentials are there?

Answer 42

1. excitatory postsynaptic potential (EPSP) opening of Na+ or Ca2+ channels leads to depolarization of the membrane 2. inhibitory postsynaptic potential (IPSP) opening of K+ or Cl- channels leads to hyperpolarization of the membrane

Question 43

what are excitatory postsynaptic potentials?

Answer 43

they arise at synapses where the transmitter depolarizes the synaptic membrane opening of Na+ or Ca2+ channels leads to depolarization of the membrane however, a single EPSP cannot induce an action potential -- EPSPs added together can reach the threshold and trigger a postsynaptic cell

Question 44

what are inhibitory postynspatic potentials?

Answer 44

they at synapses where the transmitter hyperpolarizes the synaptic membrane opening of K+ or Cl- channels leads to hyperpolarization of the membrane so the excitatory neurons have to have a higher potential than the inhibitory neuron for an action potential to happen

Question 45

what is summation in neurons?

Answer 45

one synapse is not strong enough to reach the threshold potential in the post synaptic neuron instead, multiple inputs summate their post-synaptic potentials in the same region of the dendrite at the same time to generate an action potential generation of an action potential depends on the summation of EPSPs and IPSPs so ultimate, the algebraic sum of all the EPSPs and IPSPs has to raise the membrane potential to the threshold potential for an action potential to occur however, if the IPSPs prevail, then the post-synaptic cell will be “silent”

Question 46

what is spatial summation?

Answer 46

*many* presynaptic terminals when stimulated at the *same time *can add up to exceed the threshold potential so it is the effect of triggering an action potential in a neuron from one or more presynaptic neurons

Question 47

what is temporal summation?

Answer 47

rapid successive discharges from a *single* presynaptic terminal can add up to exceed the threshold potential

Question 48

what are modulatory transmitters?

Answer 48

modulatory transmitters alter the response of fast ionotropic transmitter actions they mediate by altering the opening states of K+ or Ca2+ channels by altering membrane potential and the refractive period so they can keep the membrane depolarized or hyperpolarized even after the initial impulse ends ex. excitatory synaptic inputs from cerebral cortex to motor neuron are modulated by slow modulatory synaptic inputs from brain stem (degree of motivation) determining the speed of the movement

Question 49

what is the function of inhibitory synapses?

Answer 49

they maintain homeostasis!! they dampen the excitation that could lead to neuronal damages they're important for streamlining relevant and precise sensory information they're also important for locomotion note: drugs against epilepsy usually targets inhibitory transmitters and increase their effect

Question 50

what is disinhibition?

Answer 50

when 2 inhibitory neurons coupled in series increase the activity of an excitatory neuron

Question 51

what is strychnine?

Answer 51

it blocks inhibitory glycinergic synapses and causes life threatening muscle spasms

Question 52

what is synaptic plasticity?

Answer 52

life experiences change the nervous system! the brain can change and adapt to new information and also there is the basis of memory, acquisition of motor and cognitive skills plasticity is broadly categorized into short and long term plasticity

Question 53

what is the mechanism of synaptic plasticity?

Answer 53

1. presynaptic terminal releases more/less neurotransmitter in response to an action potential OR 2. postsynaptic neuron increases/decreases its response to the transmitter

Question 54

what is short term plasticity?

Answer 54

changes in synaptic strength that occur on a sub-second time scale and reverts to “normal” soon afterwards 1. facilitation 2. potentiation 3. short term depression

Question 55

what is facilitation?

Answer 55

increased transmitter release by presynaptic neuron

Question 56

what is potentiation?

Answer 56

increased synaptic efficiency even after the stimulation ends

Question 57

what is short term depression?

Answer 57

weaker post-synaptic response

Question 58

what is long term plasticity?

Answer 58

it can last anywhere from minutes to hours, days, or years this is the dominant model for how the brain stores information! 1. long term potentiation 2. long term depression

Question 59

what is long term potentiation?

Answer 59

persistent strengthening of a synaptic connection

Question 60

what is long term depression?

Answer 60

long-term weakening of a synaptic connection

Question 61

what are the steps in long-term potentiation?

Answer 61

1. glutamate is released from the presynaptic neuron and acts on two receptors: AMPA and NMDA 2. Na+ flows into the postsynaptic neuron only through the AMPA receptor (since Mg2+ blocks NMDA receptor ) 3. depolarization of the postsynaptic cell removes Mg2+ block on NDMA receptor 4. Na+ and Ca2+ flow through NMDA receptor into postsynaptic neuron 5. [Ca2+] initiates activation of protein kinase-mediated signaling cascades 6. this increases the number and sensitivity of AMPA receptors

Question 62

what is late phase long-term potentiation?

Answer 62

when sustained activation of the early phase kinases initiates signal cascades leading to protein synthesis, morphological changes of the neuron, and gene expression this includes both postsynaptic changes and presynaptic changes 1. postsynaptic changes = increased dendritic area and spines which increase postsynaptic sensitivity or increase in AMPA receptors inserted in the postsynaptic membrane 2. presynaptic changes = increased binding and release of neurotransmitter vesicles from the presynaptic membrane or increase in the total number of presynaptic neurotransmitter vesicles these are the underlying mechanisms for learning and addiction!

Question 63

what is long term depression?

Answer 63

long term depression decreases the efficacy of a synapse  observed in cerebellum (motor learning), hippocampus (memory decay), the visual cortex, and the prefrontal cortex mechanism proceeds due to low frequency stimuli and a slow rise in postsynaptic [Ca2+] example: activation of phosphatase-mediated signaling resulting in the internalization of AMPA receptors

Question 64

what is the MOA of lead poisoning?

Answer 64

Blocks NMDA receptors limiting synaptic plasticity and memory lead accumulates around nerves causing them to degenerate and demyelinate. It also inhibits heme synthesis pathway leading to the build up of substrate δ-Aminolevulinic acid (ALA) which is directly toxic to neurons. Thirdly it blocka NMDA receptors. Effects are particularly potent among children since it interferes with normal neurologic development. this causes acute encephalopathy through multiple mechanisms 

Question 65

what is the correct order in a normal flexion reflex?

Answer 65

1. AP in sensory afferent neuron 2. EPSP in interneuron 3. AP in interneuron 4. EPSP in motor neuron 5. AP in motor neuron 6. AP in flexor muscle 7. contraction of flexor muscle

Question 66

at the negative resting membrane potential, the NMDA receptors little ionic current because.....

Answer 66

they are blocked with Mg+2

Question 67

what creates the barrier that is the reason for chemical synapse discontinuity?

Answer 67

the synaptic cleft

Question 68

what is the most direct cause for the presynaptic vesicles to fuse with the presynaptic membrane and release a neurotransmitter into the synaptic cleft?

Answer 68

release of calcium ions into the presynaptic neuron terminal

Question 69

______ receptor has a direct, mechanical response to the binding of a neurotransmitter?

Answer 69

ionotropic

Question 70

_____ is the major inhibitory neurotransmitter in the CNS

Answer 70

GABA

Question 71

when would you expect to see an increase in Cl- ions in the neurons? during EPSP or IPSP?

Answer 71

IPSP when Cl- enters the neuron, it hyperpolarizes the neuron and it's inhibitory

Question 72

long term depression involves.....

Answer 72

protein phosphatase mediated internalization of the AMPA receptors