Central Neurotransmitter System

Question 1

There are two major types of neurotransmitters, small molecules are one of them, list some examples:

Answer 1

Acetylcholin
Amino acids: Glutamate, GABA, glycine
Biogenic amines: dopamine, norepi, serotonin

Question 2

There are two major types of neurotransmitters, neuropeptides are one of them list their characteristics:

Answer 2

More than 100 different peptides (diverse). Typically 3-36 AA long. They are Nonclassical neurotransmitters.

Question 3

Which type of neurotransmitter can respond to increased demand rapidly? Why?

Answer 3

Small molecule neurotransmitters because they are synthesized in nerve terminals

Question 4

How are small molecule neurotransmitters synthesized?

Answer 4

They are synthesized within presynaptic terminal and packaged into vesicle by specific transport protein in the vesicle membrane. They are classified under slow axonal transport since the enzymes to make them are synthesized in the body and transported down to the synaptic site.

Question 5

Which type of neurotransmitter can NOT respond to increased demand rapidly?

Answer 5

Neuropeptide neurotransmitters because they are synthesized in the cell body and must be transported the entire length of the axon to release site by fast axonal transport. Their release must be carefully regulated to avoid depletion.

Question 6

What are ionotropic neurotransmitter receptors? How many subunits do they typically have?

Answer 6

Ligand-gated ion channels.

4-5 subunits that each contain 3 or 4 transmembrane domains

Question 7

What are metabotropic neurotransmitter receptors?

How many subunits do they typically have?

Answer 7

G-protein coupled receptors

Monomeric proteins containing 7 transmembrane domains. Wide variety for most neurotransmitters

Question 8

In the PNS where is acetylcholine used?

Answer 8

At the neuromuscular junction. Synapses in ganglia of visceral motor system.

Question 9

In the central nervous system where is acetyl choline used?

Answer 9

Interneurons in brainstem and forebrain. Large neurons in the basal forebrain that project to cerebral cortex.

Question 10

The function of acetylcholine in the CNS is not well understood but what functions in the CNS is it believed to control?

Answer 10

Attention, arousal, reward, plasticity. Enhances sensory functions upon wakening. Damage to cholinergic system is associated with the memory defects in AD.

Question 11

What effect does sarin gas have on humans?

Answer 11

It blocks acetylcholinesterase and causes ACh to accumulate depolarizing the target cell at cholinergic synapses and making it refractory to subsequent ACh release. At NMJ it results in paralysis

Question 12

There are metabotropic ACh receptors as well as ionotropic receptors. In the CNS what do they do?

Answer 12

They mediate most ACh effects in the brain and are highly expressed in the forebrain. They of course are also present in peripheral ganglia where they mediate responses of autonomic effector organs.

Question 13

What does Atropine do?

What does scopolamine do?

Answer 13

It is an ACh antagonist and causes pupil dilation.
It is another ACh antagonist used to treat motion sickness. There are two different antagonists for different receptors that bind the same neurotransmitter, this shows the diversity of the receptors how they elicit different functions.

Question 14

What is Myasthenia Gravis? What are the symptoms?

Answer 14

It is an autoimmune disease where immunoglobulins bind to the muscle nAChR causing increased turnover of the receptors. It ultimately alters the structure at the NMJ. Symptoms include muscle fatigability that worsens late in the day or after repetitive exercise, but typically improves with rest. (diplopia, ptosis, dysarthria, dysphagia, etc). Symptoms are only in the PNS because nAChR is only in the PNS.

Question 15

Describe the AP in the postsynaptic cell:

Answer 15

The probability that a presynaptic action potential will elicit a postsynaptic muscle action potential is reduced. During repeated stimulation, compound AP in the muscle decreases in size (fatigues)

Question 16

How is Myasthenia Gravis treated?

Answer 16

Cholinesterase inhibitors improve symptoms. Thymectomy can help put it in remission. Corticosteroids. Immunosuppressants.

Question 17

What is the most prominent neurotransmitter for normal brain function? (hint: nearly all excitatory neurons in brain use this as their transmitter)

Answer 17

Glutamate.

Question 18

Glutamate can be excitotoxic, when does this happen?

Answer 18

When there is high extracellular concentrations of glutamate. Excessive activation of glutamate receptors can excite neuron to death. It is thought to cause neuronal damage during strokes b/c O2 deprivation slows down glutamate reuptake.

Question 19

Can glutamate cross the blood brain barrier?

Answer 19

NO! But glutamine can!

Question 20

Where is glutamate synthesized and from what precursor? Describe the process of release and reuptake as well:

Answer 20

In the nerve terminal from glutamine. It can also be synthesized by transamination of A-ketoglutarate (CAC intermediate). It is packaged into synaptic vesicles by a vesicular glutamate transporter, removed from synaptic cleft by high affinity glutamate transporters on both the nerve terminal and nearby glial cells. In glial cells, glutamate is converted into glutamine and then transported out of the cell and back into nerve terminals.

Question 21

There are three types of ionotropic glutamate receptors, what are they?

Answer 21

NMDA, AMPA, kainate. These are all excitatory cation-selective (Na) channels.

Question 22

What is unique about NMDA receptors?

Answer 22

Ca can pass through them, ion flow is voltage dependent because of Mg binding, glycine binding is required to open channel.

Question 23

What are the major inhibitory neurotransmitters in the CNS?

Answer 23

GABA and glycine. GABA is widely distributed in the brain, used by local interneurons and Purkinje cells of the cerebellum. Glycine is predominantly used at synapses in spinal cord.

Question 24

Describe synthesis, packaging, and removal of GABA:

Answer 24

It is synthesized in nerve terminals from glutamate, packaged into synaptic vesicles by the vesicular inhibitory amino acid transporter. It is removed from synaptic cleft by specific transporters on nerve terminals and nearby glia.

Question 25

What can decreased GABA function cause?

Answer 25

Epilepsy

Question 26

Describe synthesis, packaging, and removal of glycine:

Answer 26

It is synthesized in nerve terminal from serene. It is package into synaptic vesicles by the vesicular inhibitory amino acid transporter, removed from synaptic cleft by specific transporters on nerve terminals and nearby glia.

Question 27

What does excess synaptic glycine cause?

Answer 27

Neonatal disease characterized by lethargy and mental retardation.

Question 28

There are 2 ionotropic GABA (a and c) and 1 glycine receptors, what do they function to do?

Answer 28

They are inhibitory chlorine channels

Question 29

GABA receptor agonists enhance GABAergic transmission, what are two examples? What can inhibitors of GABA reuptake do?

Answer 29

Benzodiazepines (valium) used as tranquilizers. Barbituates (phenobarbital) used as anesthetics to control epilepsy.
They can treat anxiety and panic disorders.

Question 30

What is strychnine, what is it used for?

Answer 30

It is a glycine receptor antagonist. It causes overactivity in spinal cord and brainstem leading to seizure, it is only used to poison rodents.

Question 31

GABA and Glutamate are made everywhere and have receptors everywhere. In contrast the Biogenic amines are synthesized and sensed in specific locations. What does this implication lead to?

Answer 31

It is what causes specific psychological issues when the other biogenic amines not balanced. The GABA and glutamate is less specific and more broad and thus have less psychological issues associated with them (except epilepsy).

Question 32

Aminergic (biogenic amines) neurons project widely in the brain and help modulate intensity of what?

Answer 32

More specific neuronal signals. The are used by relatively few neurons in the brain but very important to mental health.

Question 33

Describe synthesis, packaging, and removal of biogenic amines:
What type of receptors do they have?

Answer 33

They are synthesized in nerve terminals, packaged via vesicular monoamine transporter (VMAT), removed by reuptake into nerve terminals.
They have metabotropic receptors (serotonin also has ionotropic)

Question 34

Dopamine receptors found in the substantia nigra, what is the function of this area? What disease is associated with their degeneration? How is it treated?

Answer 34

Substantia nigra; sends projections to striatum. Function to coordinate body movements. In Parkinson’s disease these neurons degenerate leading to motor dysfunction. Parkinson’s patins are treated with the dopamine precursor, L-DOPA to increase dopamine levels in the striatum

Question 35

Dopamine receptors are found in the midbrain with projection from ventral segmental area to ventral parts of striatum, what do these structures function to do? What can alter their function?

Answer 35

Involved in motivation, reward and punishment. Addictive drugs such as cocaine raise dopamine levels by interfering with reuptake by dopamine transporters.
Some minor projection go to the cortex and are involved with impulsivity and emotional behavior.

Question 36

Norepinephrine containing neurons send their projections from locus coeruleus to a variety of forebrain and brainstem targets, what do they function to do?

Answer 36

Influences sleep and wakefulness, attention, and feeding behavior.
In the PNS it is prominent in sympathetic ganglion cells. It is the major transmitter of sympathetic motor system.

Question 37

How do dopamine receptors act?

Answer 37

By inhibiting adenylyl cyclase. Antagonists of receptors in medulla used as anti-emetics to treat nausea and vomiting.

Question 38

Serotonin containing neurons are found in Raphe nuclei in upper brainstem; project widely to the forebrain and also to brainstem: what do they function to do?

Answer 38

Implicated in regulation of sleep, eating, arousal and wakefulness. Drugs used to treat depression and anxiety act on serotonergic neurons (SSRI)

Question 39

How do anti-psychotic drugs work?

Answer 39

Block dopamine receptors suggesting excess dopamine release may cause some psychotic illnesses such as schizophrenia.

Question 40

How do anti-anxiety drugs work?

Answer 40

MAO (monoamine oxidase) inhibitors block breakdown of biogenic amines. Inhibitors of serotonin receptors are also anti-anxiety.

Question 41

How do anti-depressants work? (there are 3 classes)

Answer 41

MAO inhibitors block breakdown of biogenic amines.
Tricyclic anti-depressants block reuptake of NE and 5HT (serotonin)
Serotonin reuptake inhibitors (Prozac) act specifically on serotonin transporters.

Question 42

What are peptide neurotransmitters involved with?

Answer 42

Modulating emotions, perception of pain, and responses to stress. Their biological activity is dependent on their amino acid sequence.

Question 43

How are neuropeptides synthesized and processed?

Answer 43

They are pre-propetides in the ER of the neuronal cell body, processed into pro peptides in ER by removal of ER targeting signal, and final processed to individual active peptides in vesicles after they bud from trans Golgi. Individual pro peptides can give rise to multiple active peptides within a single vesicle.

Question 44

How do opioid peptides work?

Answer 44

They are widely distributed throughout the brain and tend to be depressants and can act as analgesics.

Question 45

There is a great summary slide

Answer 45

at the end of lecture