Lecture 10: Principle of Synaptic Transmission

What are the different modes of neuronal communication?

• chemical synaptic transmission

• electrical synaptic transmission

• interneuronal communication (gases, hormones, and endocannabinoids)

• autocrine and paracrine signaling

What did the Neuron Doctrine say?

information storage in the brain results from alteration in synaptic connections between neurons (communicate by contact, not continuity)

True or False: By the late 19th century, scientists recognize that information transfer from one neuron to the other occurs at the specialized sites of contact termed “synapse”.

true

Who coined the term “synapse”?

Charles Sherrington

What are the types of synapses?

chemical and electrical synapses

Who founded chemical synapses?

Otto Loewi (heart) in Austria

Who founded electrical synapses?

Ewin Furshpan and David Potter (crayfish) at Harvard U

What are some of the landmarks in electrical synapses?

• gap junctions

• connexons

What are some of the landmarks in chemical synapses?

• synaptic vesicles

• postsynaptic dendrite

True or False: Electrical synapses are found in cardiomyocytes and many types of smooth muscle cells where contractile activity among a group of cells is important. They are found in neurons important for synchronous oscillation and synaptic integration.

true

True or False: There are microfilaments (actin), crosslinking proteins (such as actinin), and gap junction channel proteins (such as connexin 43) at gap junction channels.

true

What type of channels are electrical synapses composed of?

gap junction channels

What do gap junction channels do?

passes small molecules (less than 1 kDa) and ions in both directions

How many connexons per channel?

2 connexons per 1 channels

How many connexins per connexon?

6 connexins per 1 connexon

What is the diameter of gap junction pores?

1-2 nm

True or False: In the mammalian CNS, there are a greater number of chemical synapses compared to electrical synapses.

true

True or False: Electrical synapses have no synaptic delay and have very fast transmission.

true

True or False: An action potential fires in Neuron 1 (presynaptic neuron). The resulting large PSP in the Neuron 2 (post synaptic neuron) generates a smaller PSP in Neuron 1 (presynaptic neuron).

true

What are the indirect pieces of evidence for chemical synaptic transmission?

• Claude Bernard (1849) - curare (a poison in arrows) blocks nerve to muscle signaling

• Thomas Elliot (1900) - epinephrine contracts smooth muscle deprived of nerve inputs

• Henry Dale (early 1900) - British pharmacologist discovers that adrenaline injection doesn’t affect the heart rate of a cat, which had a prior injection of the drug that slows the heart rate

Who discovered the direct piece of evidence for chemical synaptic transmission?

Otto Loewi and Sir Henri Dale

Briefly describe the intrinsic cardiac conduction system.

cardiomyocytes in the SA node spontaneously depolarize—resulting in contraction of approximately 100 times per minute (the primary pacemaker)

Contraction (excitation) starts from spontaneous depolarization of which what in the heart? Then wave of excitation moves to what?

• spontaneous depolarization of the sinoatrial node in the atria

• wave of excitation moves to the ventriculus

What is the native cardiac rate?

100 beats per minute

What is the average resting cardiac rate in adult humans?

70 beats per minute

Why is the native cardiac rate and resting cardiac rate different?

• sympathetic nerve fibers speed the beating of the heart by norepinephrine

• parasympathetic nerves slow the beating by acetylcholine

Briefly describe Otto Loewi’s study.

“vagusstoff” released from the vagal nerve slows the heart beat of an isolated frog heart

Briefly describe Sir Henry Dale’s study.

• identified that the heart-slowing chemical is ACh

• refined the understanding of acetylcholine’s role as a chemical neurotransmitter in the heart and the nervous system

True or False: Pacemaking slows within 100 ms of stimulation of parasympathetic vagal nerves (inhibitory) which releases ACh.

true

How does ACh slow the beating of the heart?

ACh activates muscarinic ACh receptors, which activate G-protein coupled inwardly rectifying potassium currents (GIRK)—leading to hyperpolarization

Briefly describe the neuromuscular junction (NMJ).

• occur between axons of neurons and muscle

• mediate fast and reliable synaptic transmission

• are large synapses

What did Bernard Katz’s studies establish?

studies of NMJ established principles of synaptic transmission

What are the different types of chemical synapses in the CNS?

• axodendritic

• axosomatic

• axoaxonic

• excitatory (Gray’s Type I)

• inhibitory (Gray’s Type II)

• dendrodendritic

List the classifications of neurons based on neurotransmitter type. Are they excitatory or inhibitory?

• glutamatergic: glutamate at excitatory synapses

• GABAergic: GABA at inhibitory synapses

• cholinergic: ACh at synapses (excitatory or inhibitory based on the postsynaptic receptors)

• dopaminergic: dopamine at synapses (excitatory or inhibitory based on the postsynaptic GPCR)

• serotonergic: serotonin at synapses (excitatory or inhibitory based on the postsynaptic GPCR)

True or False: Most synaptic transmission in the mature human nervous system is chemical.

true

Briefly describe the chemical synaptic clefts.

• 20-50 nm wide

• extracellular matrix proteins

Briefly describe secretory granules.

• dense core vesicles

• 100 nm diameter

• soluble proteins/neuropeptide transmitters

Briefly describe synaptic vesicles.

• 50 nm diameter

• classical neurotransmitters

• recycling

What are the 2 different membrane differentiations in chemical synapses?

• active zone

• postsynaptic density

True or False: Larger synapses have more active zones.

true

List the steps in chemical transmission.

1. synthesis of neurotransmitters in presynaptic neuron

2. storage of neurotransmitters in presynaptic terminal (by loading them into synaptic vesicles)

3. release of neurotransmitters into the synaptic cleft

4. binding of neurotransmitters to postsynaptic receptors (causing postsynaptic biochemical/electrical response)

5. termination of the released neurotransmitter action (by removing them from synaptic cleft)

List the steps in the life cycle of a classic neurotransmitter/homeostatic feedback mechanisms.

1. accumulation of precursor amino acid X into a neuron

2. amino acid precursor is metabolized sequentially to yield mature neurotransmitter

3. Z transmitter is then accumulated into the synaptic vesicles by vesicular transporter where it is poised to be released and protected from degradation

4. once released, the transmitter can interact with postsynaptic receptors or auto receptors that regulate transmitter release, synthesis, or firing rate

5. transmitter actions are terminated by means of a high-affinity membrane transporter that usually is associated with the neuron that released the transmitter

6. once taken up, it is subject to metabolic inactivation or the transmitter actions can be terminated by diffusion from the active site or accumulation into glia through a membrane transporter

What are the essential components of chemical transmission?

• neurotransmitters

• neurotransmitter receptors

True or False: Neurotransmitters transmit information between neurons and are an essential link between neurons and effector cells.

true

True or False: Neurotransmitter receptors initiate postsynaptic chemical and electrical responses.

true

What can defects or dysregulation in neurotransmitters and/or neurotransmitter receptors cause?

many neurological and psychiatric disorders

What is neuropharamacology?

effect of drugs on nervous system tissue

What are receptor antagonists? Give an example.

• inhibitors of neurotransmitter receptors

• curare for nicotinic acetylcholine receptor

What are receptor agonists? Give an example.

• mimics actions of naturally occurring neurotransmitters

• nicotine for nicotinic acetylcholine receptor

Describe tetanus.

• caused by (general): a dysfunction in neurotransmitter termination in the NMJ

• symptoms: muscular spasms, hypertonia (stiff muscles), and lock jaw

• caused by (specific): tetanospasmin from Clostridium tetani (bacteria) blocks GABA and glycine release from inhibitory interneurons in the spinal cord