Synaptic Transmission

what is a synpase?

junction between a presynaptic and a postsynaptic neuron

presynaptic and postsynaptic neurons do not actually make physical contact. therefore, there is no direct electrical transmission of the signal from one neruon to another. what happens instead?

presynaptic neuron(s) release a chemical neurotransmitter that binds to receptors on the postsynaptic neuron to initiate a new action potential.

the process of presynaptic neuron(s) releasing a chemical neurotransmitter that binds to receptors on the postsynaptic neuron to initiate a new action potential is called…?

transduction

what are the different anatomic variations of synapses?

Presynaptic Events in transmission occur in

axon terminals

axon terminals contain many _______, each containing a _________

axon terminals contains many synaptic vesicles, each containing a quantum (~3000-5000 molecules) of neurotransmitte

what are some examples of neurotransmitters?

acetylcholine, norepinephrine, glutamine, serotonin, glycine, etc.

axon terminals expand into ________ that contain numerous ________ that contain the chemical ________- that will excite the postsynaptic cell

knobs (terminal boutons)

small membrane-bound synaptic vesicles (~ 50 nm diameter)

neurotransmitters

many synpatic vesicles found in knobs lie close to what zone?

specialized zone in the terminal called active zone

what happens in response to an action potential arriving at the terminal?

vesicles fuse to plasma membrane in active zone realasing their content

walk through the cycle of neurotransmitter release from presynaptic neurons

1. Each synaptic vesicle is filled with a quantum of neurotransmitter ( about 3000-5000 molecules).

2. Vesicles then move toward the plasma membrane in the active zone

3. Where they are “docked” and “primed” and ready for fusion with the plasma membrane

each synaptic vesicle is filled with

a quantum of neurotransmitter (3000-5000 molecules)

docking and priming involve 3 snare proteins that do what

a coiled-coil that holds the vesicle close to the plasma membrane and prepares it for fusion

what are the 3 snare proteins invovled in docking and priming?

• synaptobrevin

• SNAP25

• syntaxin

(Many of these proteins are the same as those involved in non-synaptic vesicle release such as the exocytosis of peptide hormones)

what is fusion triggered by?

presynaptic action potential that also opens voltage-gated Ca++ channels located in the active zone of the plasma membrane.

what is a 4th protein that binds to the vesicle membrane and prevents spontaneous fusion of the vesicle with the plasma membrane under resting conditions?

synaptotagmin

what happens during fusion?

1. synaptotagmin binds to vesicle memrane and prevent spontaneous fusion of vesicle with plasma membrane under resting conditions

2. upon activation by an action potential, Ca++ entering the cell binds to synaptotagmin, causing it to change its conformation and interactions with the snare proteins to promote vesicle fusion and the release of neurotransmitter

describe the steps in the release of neurotransmitter from presynaptic terminal

1. arrival of the action potential at the axon terminal also causes the opening of local voltage-gated Ca++ channels

2. Ca++ enters the cell and binds to a fourth protein called synaptotagmin

3. this triggers fusion of the vesicle with the axon membrane and the release of the neurotransmitter into the synaptic cleft: = calcium-dependent exocytosis

4. ACh is rapidly degraded by the enzyme AChesterase present in the cleft

5. empty vesicles are recovered by cell and recycled

what happens to synaptic vesciles after release of neurotransmitter into the synaptic cleft?

SVs are endocytosed (1, 2), fuse with the endosome (3) , and ultimately pinched off to form a new vesicle (4).

the presynaptic cell stores transmitter in

membrane-bound synaptic vesicles (SVs)

A rise in intracellular Ca2+ concentration promotes

1. SV fusion with the plasma membrane

2. release of a quantum of transmitter into the synaptic cleft

the essential nature of the three SNARE proteins is underscored by the fact that each can be hydrolyzed by one of several deadly neurotoxins produced by the anaerobic bacterium, _______________.

Any one of these toxins blocks exocytosis, paralyzing muscle and leading to respiratory failure and death if untreated. Humans are most commonly exposed through ingestion of improperly canned foods

Clostridium botulinum

Released ACh is rapidly destroyed by the enzyme _______ which cleaves it into two inactive components.

ACH-esterase

what are some of the numerous neurotransmitters expressed in peripheral and central nervous system neruons. what are some common ones?

• acetylcholine (A neurotransmitter used by neurons in the PNS and CNS in the control of functions ranging from muscle contraction and heart rate to digestion and memory)

• norepinephrine, (epinephrine)

• serotonin.

• dopamine.

• GABA. (-aminobutyric acid)

• glutamate..

• endorphin

(postsynaptic events) Once neurotransmitter is released into the synaptic cleft, it is available to bind receptors on the postsynaptic nerve or ______ to elicit a post-synaptic or _______. These cells have many receptors in the vicinity of the presynaptic active zone

neuromuscular junction (NMJ)

end-plate potential

what are 2 possiblee fates of neurotransmitters in the cleft during postsynaptic events?

1. hydrolyzed by extracellular enzymes present in cleft (acetylcholine esterase)

2. transported back into terminal via high-affinity transporters (repackaged into SVs for reuse)

why does the cell depolarize even when permeability of Na and K+ is equal during postsynaptic events?

since the resting potential (Em) of the postsynaptic cell is far from the ENa and close to EK, the electrical driving force on Na+ is greater than that for K+. This causes the inward Na+ current to be much larger than the outward K+ current, and the cell depolarizes even when the permeability is equal.

the response of the postsynaptic neuron is a depolarization called an

excitatory post-synaptic potential or EPSP

what does it mean that excitatory post-synaptic potential or EPSP are graded?

their amplitude depends upon:

• how many quanta of ACh were released by the presynaptic cell

• how much was destroyed in the cleft by the esterase

• how many ACh receptors are occupied by 2 ACh molecules and for how long

what are possible responses to excitatory post-synaptic potential or EPSP?

• subthreshold EPSP

• suprathreshold EPSP

role of EPSP

trigger opening of voltage gated channel (to allow for action potential in the postsynaptic neuron, EPSP itself is NOT an action potential)

• chemically induced by neurotransmitters

• depolarize the postsynaptic cell enough to reach the threshold of the voltage-gated channels and produce an action potential

what are examples of neuroinhibitors?

lambda-aminobutyric acid or GABA

what does lambda-aminobutyric acid or GABA (neuroinhibitor) do?

• binds to GABA receptors on the postsynaptic membrane and opens Cl- channels

• Cl- diffuses into postsynaptic cell and makes Em more polar (hyperpolarized)

  • moves further from threshold causing inhibition

what provide a mechanisms to control the excitability of a postsynaptic neuron?

inhibitory postsynaptic potentials

what is a ionotropic receptor?

transmitter binds → channel opens → ionic current flows

very rapid

what are metabotropic receptors?

transmitter binds → G-protein activated → G-protein subunits/2nd messengers are activated → ion channel opens → ionic current flows

slower

what factors determine post-synaptic neurons being either excited or inhibited?

• type of neurotransmitter

• type of change in permeability of post-synaptic membrane

How do we increase the probability of a postsynaptic action potential?

summation

what are types of summation?

spatial summation

temporal summation

what is spatial summation?

1. simultaneous stimulation by several presynaptic neurons

2. EPSPs spread from several synapses to axon hillock

3. postsynaptic neuron fires

what is temporal summation?

1. high frequency stimulation by 1 presynaptic neuron

2. EPSps spread from 1 synapse to axon hillock

3. postsynaptic neuron fires