Synaptic Transmission

Blazin

What were the "sparkers" and "soupers" debating?

Whether communication between neurons was electrical (sparkers) or chemical (soupers).

What did Otto Loewi's frog-heart experiment demonstrate?

Stimulating the vagus nerve slowed one heart; transferring fluid from around that heart to another heart also slowed the second heart, providing evidence that a chemical messenger mediated the effect.

What neurotransmitter was identified in connection with Loewi's experiment?

Acetylcholine (ACh).

Who shared the 1936 Nobel Prize for discoveries related to chemical transmission?

Otto Loewi and Henry Dale.

What happened when Eccles attempted to support electrical transmission in the CNS?

His evidence instead supported chemical transmission, and he changed his position.

What exactly is a synapse?

The entire communication structure consisting of the presynaptic terminal + synaptic cleft + postsynaptic site.

What is the synaptic cleft?

The space between the presynaptic and postsynaptic cells.

What structures are typically presynaptic and postsynaptic?

Presynaptic → axon terminal. Postsynaptic → dendrite or soma.

Define neurotransmitter.

A chemical released by a presynaptic neuron into the synaptic cleft that affects the postsynaptic neuron.

What is the major excitatory neurotransmitter discussed in the course?

Glutamate.

What is the major inhibitory neurotransmitter discussed in the course?

GABA.

What are the three catecholamines discussed in lecture?

Dopamine, norepinephrine, and epinephrine.

What amino acid is the precursor for the catecholamines?

Tyrosine.

What is the catecholamine synthesis sequence emphasized in lecture?

Tyrosine → L-DOPA → dopamine → norepinephrine → epinephrine, with available enzymes determining how far synthesis proceeds.

What major functions of dopamine were emphasized?

Reward/pleasure/addiction circuitry and motor movement.

What dopamine-related disorder was discussed?

Parkinson's disease, involving degeneration of dopamine-producing cells and resulting especially in motor disruption.

What major function of norepinephrine was emphasized?

Mood regulation.

What is another name for epinephrine, and what function was emphasized?

Adrenaline; involved in stress and autonomic nervous-system activity.

What neurotransmitter is also called 5-HT?

Serotonin.

What amino acid is the precursor for serotonin?

Tryptophan.

What functions of serotonin were emphasized?

Mood, sleep, and appetite.

What major functions of acetylcholine were emphasized?

Muscle/motor control and learning/memory.

What neurotransmitter system is affected early in Alzheimer's disease according to lecture?

Acetylcholine.

What are the two classes of unconventional neurotransmitters discussed?

Soluble gases and endocannabinoids.

What makes retrograde transmission unusual?

The signal travels postsynaptic → presynaptic, rather than the usual presynaptic → postsynaptic direction.

What are neuropeptides?

Large-molecule neurotransmitters consisting of short chains of amino acids; the lecture described them as around 10 or fewer amino acids.

What are endorphins?

Endogenous opioid neuropeptides that can reduce/blunt pain.

What is a receptor?

A site on a neuron where a neurotransmitter binds.

What does the lock-and-key model of neurotransmitter receptors mean?

Receptors have specificity: a neurotransmitter affects a neuron only if that neuron has an appropriate receptor for it.

What is a ligand?

A molecule that binds to another molecule/receptor. Neurotransmitters and drugs can act as ligands.

Where are small-molecule neurotransmitters synthesized?

In the axon terminal, using building blocks derived from food/blood.

Where are neuropeptides synthesized?

In the cell body, like proteins.

How do neuropeptides made in the soma reach the axon terminal?

They are transported along microtubules.

What packages neurotransmitters into vesicles?

The Golgi complex.

What is a quantum in synaptic transmission?

A discrete package of neurotransmitter contained/released in a vesicle.

What is coexistence?

A single neuron can contain and release more than one neurotransmitter.

What happens FIRST when an action potential reaches the axon terminal?

The terminal depolarizes, causing voltage-gated Ca2+ channels to open.

After voltage-gated Ca2+ channels open, what happens?

Ca2+ enters the presynaptic terminal.

What does Ca2+ entering the presynaptic terminal cause?

Synaptic vesicles fuse with the presynaptic membrane and release neurotransmitter into the synaptic cleft.

Define exocytosis in synaptic transmission.

The Ca2+-triggered process in which neurotransmitter-containing vesicles fuse with the presynaptic membrane and release their contents into the synaptic cleft.

Give the neurotransmitter-release sequence from AP arrival through release.

AP arrives → terminal depolarizes → voltage-gated Ca2+ channels open → Ca2+ enters → Ca2+ acts on vesicles → vesicles fuse with presynaptic membrane → neurotransmitter released into cleft.

What is an ionotropic receptor?

A receptor directly associated with a chemically/ligand-gated ion channel.

What opens a chemically gated ion channel?

The presence/binding of a chemical ligand, such as a neurotransmitter.

Voltage-gated vs chemically gated channel?

Voltage-gated → responds to membrane voltage. Chemically gated → responds to a chemical/neurotransmitter binding.

Does a neurotransmitter pass through an ionotropic receptor into the postsynaptic neuron?

NO. It binds to the receptor and causes the associated ion channel to open/close. The ions, not the neurotransmitter, cross through the channel.

How can glutamate produce an EPSP through an ionotropic receptor in the lecture model?

Glutamate binds → chemically gated Na+ channel opens → Na+ enters → depolarization/EPSP.

How can GABA produce an IPSP through ionotropic receptors?

GABA can open Cl− or K+ channels, producing an inhibitory postsynaptic effect.

What are the general characteristics of ionotropic receptor effects?

Rapid (~10 ms), short-lasting, and localized.

What is a metabotropic receptor associated with?

A G protein and signaling machinery rather than directly being an ion channel.

What happens after neurotransmitter binds a metabotropic receptor?

Neurotransmitter binds → G protein activated/subunit separates → it affects intracellular targets, which may include ion channels or second-messenger production.

In metabotropic signaling, what is the first messenger?

The neurotransmitter.

What is the role of a second messenger?

It participates in intracellular signaling cascades and can produce widespread cellular effects, potentially including effects on the nucleus, DNA, and protein production.

What are the general characteristics of metabotropic receptor effects?

Slower onset (~30 ms), longer-lasting (seconds to minutes or even hours), and more widespread.

Compare ionotropic and metabotropic receptors in one line.

Ionotropic = direct ion channel, fast/brief/local. Metabotropic = G protein/second messenger, slower/longer/widespread.

Is glutamate always ionotropic and GABA always metabotropic?

No. Neurotransmitters can have different receptor subtypes; transmitters can have both ionotropic and metabotropic receptors.

Where are autoreceptors located?

On the presynaptic membrane.

What does an autoreceptor bind?

The neuron's own neurotransmitter.

What is the major function of an autoreceptor?

It provides feedback about neurotransmitter levels in the synaptic cleft and can regulate subsequent production/release.

Are autoreceptors the same as reuptake sites?

NO. Receptors bind neurotransmitters; reuptake sites transport neurotransmitter back into the presynaptic terminal.

What are the two major neurotransmitter-deactivation mechanisms discussed?

1. Reuptake. 2. Enzymatic degradation.

What is reuptake?

Neurotransmitter is taken back into the presynaptic terminal, where it can be reused/repackaged or otherwise processed.

What is enzymatic degradation?

Enzymes break down neurotransmitter molecules, ending their activity.

What enzyme breaks down acetylcholine in the lecture example?

Acetylcholinesterase (AChE).

What structure creates an electrical synapse?

A gap junction.

How do gap junctions work?

They directly connect the cytoplasm of two cells, allowing ions/electrical charge to pass between them.

What are three characteristics of electrical synapses emphasized in lecture?

They are very fast, bidirectional, and useful for synchronizing neural activity.

Why might chemical synapses be advantageous in the brain despite being slower?

They permit more complex and subtle control through combinations of excitation and inhibition.

What is an agonistic drug effect?

It facilitates/increases the effect of a neurotransmitter.

What is an antagonistic drug effect?

It inhibits/reduces the effect of a neurotransmitter.

What are several ways a drug could act agonistically according to the lecture?

Increase synthesis, increase transmitter availability/release, block inhibitory autoreceptor action, activate/facilitate postsynaptic receptors, or block deactivation such as reuptake/degradation.

What are several ways a drug could act antagonistically?

Reduce synthesis, cause transmitter loss/destruction, block release, activate inhibitory autoreceptors, or block postsynaptic receptors.

In the lecture's schizophrenia example, why would a dopamine receptor blocker be considered antagonistic?

The hypothesis presented involves excessive dopamine action at certain synapses; blocking dopamine receptors reduces dopamine's effect.

Why is L-DOPA an agonistic/facilitating strategy in Parkinson's disease?

Parkinson's involves deficient dopamine activity; providing L-DOPA, a dopamine precursor, increases the ability of surviving cells to synthesize dopamine.

What synaptic mechanism did the professor describe for cocaine?

It blocks dopamine reuptake, causing dopamine to accumulate in the synaptic cleft.

Why does blocking dopamine reuptake increase dopamine signaling?

Dopamine remains in the synaptic cleft longer and can repeatedly interact with its receptors instead of being rapidly taken back into the presynaptic terminal.

What additional feedback occurs when synaptic dopamine becomes very high in the lecture's example?

Dopamine also binds autoreceptors, signaling the neuron to reduce further dopamine production/release.

According to the lecture, how does alcohol affect GABA signaling?

It facilitates GABA's inhibitory action at a receptor, increasing the inhibitory effect associated with Cl− channel activity.

Why can an acetylcholinesterase inhibitor increase acetylcholine signaling?

Blocking AChE prevents/decreases ACh breakdown, so ACh remains available in the synapse longer.