Neurotransmitter 2

Question 1

Modulators

Answer 1

By themselves cannot activate or inhibit neurons , they need GABA, glutamate (example) to exert their actions.
This is not the case for ACh. Even though ACh can be categorized as neurotransmitter, it can by itself excite or inhibit neurons.

Question 2

Key names of the synthesis areas of ACh, serotonin, dopamine, noradrenaline.

Answer 2

ACh : Basal forebrain
Serotonin : Raphe Nuclei
Dopamine : Ventral Tegmentum
Noradrenaline : Locus Coeruleus

Question 3

ADHD :

Answer 3

Low cortical activity in the Prefrontal cortex
People who have been diagnosed with ADHD, the optimal dose of dopamine is not there. You try to achieve the optimal dose with medication.

Question 4

Treatment for ADHD

Answer 4

Because you have low cortical activity in the prefrontal cortex , you can treat it via noradrenergic system, serotonergic system, cholinergic system and dopaminergic system.

Question 5

Parkinsons’ Disease

Answer 5

Etiology :Degeneration of cells in the substantia nigra. : Dopamine depletion.
You first have degeneration of cells in the substantia nigra and then in the ventral tegmental area.
There is less inhibition of globus pallidus because substantia nigra doesn’t excite dorsal striatum so it cannot inhibit globus pallidus and globus pallidus inhibits thalamus. So motor cortex is not activated.
So first motor dysfunctions and then cognitive dysfunctions. Less and less activation from dopamine means less activation of prefrontal cortex.
Symptoms :
Bradyakinesia : slowing/loss of movement mechanism through increase of motor threshold.
Parkinsons’ patients also have tremors.
Activating sub-thalamic nucleus via high intensity pulses works to stop it. : Deep Brain Stimulation
As I understand mainly stimulation of the subthalamic nucleus is effective for other symptoms of Parkinson’s disease such as rigidity etc..
So with deep brain stimulation you target sub thalamic nucleus.

Question 6

Dopamine Synthesis

and Noradrenaline synthesis

Answer 6

1. Tyrosine becomes DOPA by tyrosine hydroxylase.
2. DOPA becomes Dopamine by DOPA decarboxylase.
3. Dopamine is transferred into noradrenaline by dopamine B-hydroxylase.

Question 7

Cells that are stained with tyrosine hydroxylase

Answer 7

• either dopaminergic cells or noradrenergic cells.

Question 8

Cells you stain for dopamine B-hydroxylase

Answer 8

You can be sure it is noradrenaline cells and not dopamine cells.

Question 9

Dopamine Synthesis Areas :

Answer 9

1) Substantia Nigra (A9)
2) Ventral Tegmental Area
3) Olfactory Tubeculum

Question 10

Dopamine System Projections

Answer 10

1) Nigro(SN) -Striatal Projections : from substantia nigra to caudate putamen, and Nucleus Accumbens.
involved in locomotion.
2) Meso-cortical : Originates from ventral segmental area and goes to prefrontal cortex.
3) Meso-Limbic System : from ventral tegmental area to amygdala and hippocampus.

Question 11

Medial Forebrain Bundle is important for :

Answer 11

Motivation
Reward
Reinforcement
Medial Forebrain bundle comes from the VTA areas towards amygdala, hippocampus and cortical areas.
Stimulation of the medial forebrain bundle : results in dopamine in amygdala, hippocampus and cortical areas : pleasurable feelings.

Question 12

Dopamine Reuptake

Answer 12

via dopamine reuptake transporters.

Cocaine and Amphetamine blocks the reuptake.

Question 13

Functions of Nigra-Striatal Projections :

Answer 13

• From substantia nigra to striatum (caudate,putamen) and Nucleus Accumbens.
• It modulates cortical motor control and action selection.

Question 14

Functions of Meso-Cortical /Limbic Projections :

Answer 14

From ventral tegmental area to prefrontal cortex /Amygdala-Hippocampus.

Question 15

Blood-Brain Barrier and Dopamine :

Answer 15

You cannot give Dopamine pills to patients with Parkinson’s disease. Because dopamine cannot pass the blood brain barrier.
You need to give L-dopa. and it is a precursor of dopamine. L-dopa can be transferred into dopamine by DOPA decarboxylase.

Question 16

Dopamine Function

Answer 16

Dopamine is important for valuation of actions and stimuli. If you get a reward then you have dopamine activation and your valuation of your actions depends on it. Therefore it is important for optimal decision making. ‘What is the best decision’ for me. This will give you the highest dopamine, reward.
Important for reinforcement learning, you do something and you get a reward then dopamine increase and you keep doing it, so you associate things.
After a while when you get used to the association your dopamine neurons fire in response to expectation of the reward not the reward itself.
But when you don’t get a reward the neurons fire less. (even less than when they are used to getting the reward and they only fire in response to the expectation of it) this is called ‘reward prediction error’.

Question 17

Dopamine Receptors :

Answer 17

• All dopamine receptors are metabotropic so G-protein coupled.
• Therefore dopamine have diffuse and long-lasting influence.
  Two sub-groups :
• D1 like receptors :
  excitatory receptors increases cAMP (the information transfer from G-proteins to the brain)
• D2 receptors :
  Inhibitory receptors : Breaks down cAMP : so inhibits the information transfer from g-proteins to the brain.
  So if you have neuron with D1-like receptors : give dopamine and you will excite the neuron.
  If you have a neuron with D2-like receptors : give dopamine and you will inhibit the neuron.

Question 18

cAMP :

Answer 18

Second messenger that transfers information from G-proteins to the rest of the brain.

Question 19

Nigro-Striatal System Function

Answer 19

Nigro-Striatal System : From substantia nigra to striatum(globus pallidus and putamen, and nuclus Accumbens).
Dopamine release by SN : facilitates action selection and movement initiation through disinhibition of motor cortex which results in lower threshold to move.

Question 20

Nigra-Striatal System Transmitters and the pathway :

Answer 20

1. Excitation of dorsal striatum by the cortex.
2. Excitation of dorsal striatum from substantia nigra via D1 receptors. (stronger inhibition info is sent)
3. Dorsal Striatum inhibits globus pallidus. (external)
4. Normally globes pallidus is inhibitory of the thalamus but now it is inhibition is inhibited.
5. Thalamus excites the motor cortex.
   You have movement initiation and selection.
   Transmitters :
   Substantia Nigra : Dopamine
   Dorsal Striatum & Globus Pallidus : GABA (because they are inhibitory).
   Thalamus & Cortex : Glutamate because they are excitatory.

Question 21

Methylphenidate / Ritalin

Answer 21

Used in the treatment of ADHD. It contributes to the control of hyperactivity and impulse control via noradrenaline. Remember people with ADHD less activation in their prefrontal cortex. And noradrenalin increases it. So does serotonin, dopamine.
Ritalin medication has inverted U-shape of cognitive performance. So if you give little bit of Ritalin it increases the cognitive performance but if you give too much then it decreases.

Question 22

When you are away from your optimal dopamine content ?

Answer 22

While you are stressed, you have higher dopamine content. So in stressful situations if you want to go back to the optimal dopamine level then you have to block dopamine.
With aging you have less dopamine. So to have optimal level of dopamine : they have to increase dopamine.
People who are diagnosed with ADHD the dopamine can be either too much or too low.

Question 23

Where does noradrenaline synthesized ?

Where do the projections go ?

Answer 23

Locus Coeruleus

Projections go to all over the brain.

Question 24

Reuptake of Noradrenaline (Norepinephrine)

Answer 24

Reuptake via Noreadrenaline Transporter (NET)

Question 25

Major function of noradrenaline ?

Answer 25

Arousal. (in the brain)

Noradrenaline is involved in ‘fight or flight’ responses.

Question 26

Amphetamine

Answer 26

increases arousal, via stimulation of release of noradrenaline.

Question 27

Synthesis of noradrenaline (norepinephrine)

Answer 27

1. Tyrosine becomes dopamine via tyrosine hydroxylase.

2. Dopamine becomes noradrenaline via Dopamine-B hydroxylase

Question 28

• Staining for tyrosine hydroxylase

- Staining for dopamine B- hydroxylase

Answer 28

1. Tyrosine Hydroxylase stains for both dopamine and noradrenaline.
2. Dopamine B- hydroxylase stains for dopamine only.

Question 29

Where does locus coerulus located ?

Answer 29

Below the cerebellum, fourth ventricle. (Two locus coerulus areas).

Question 30

Noradrenaline / Norepinephrine Functions :

Answer 30

Outside of the the brain, noradrenaline is released by adrenal medulla into blood as a hormone. It mediates fight or flight response.
In the central nervous system it is a neurotransmitter in sympathetic nervous system. It modulates fight or flight response.
So it is involved in pupil dilation etc..
Noradrenaline is a major neuromodulator of the CNS.
It is involved in coarse behavioral state (arousal).

Question 31

Noradrenaline (Norepinephrine Receptors)

Answer 31

All noradrenaline receptors are metabotropic G-protein coupled receptors.

Question 32

The relationship between beta and noradrenaline and the heart :

Answer 32

In the heart we only have beta receptors.
Beta blockers will decrease the heart rate. It prevents the overstimulation of the heart by blocking adrenaline and noradrenaline receptors I guess.

Question 33

Noradrenaline is increased by ;

Answer 33

• Antidepressants , for instance MAO-blockers block the break down and Tricyclic antidepressants block the reuptake.
• ADHD medication such as ritualize (methylphenidate) it is a reuptake blocker
• Atomexetine : more selective reuptake blocker.
• Modafinil : amplify LC phasic responses.

Question 34

Functions of noradrenaline

Answer 34

Enhances activity in the preferred location.

Question 35

Where does serotonin synthesized ?

Answer 35

Raphe Nucleus

Question 36

Projection areas of serotonin ;

Answer 36

All over the brain. 
Hippocampus amygdala
Thalamus
Cortex
Cerebellum

Question 37

Functions of Serotonin :

Answer 37

Serotonin is involved in gut motility and vasculature.

Involved in the regulation of mood, anxiety, arousal, circadian rhythms, eating disırders, migraine, pain, drug abuse

Question 38

Serotonine reuptake via ;

Answer 38

SERT (serotonin reuptake transporters)

Question 39

Prozac

Answer 39

It is antidepressant and it works as a selective serotonin reuptake inhibitor. So it makes sure there is more serotonin.

Question 40

Where does raphe nuclei located ?

Answer 40

beneath aqueduct : dorsal raphe nuclei. Also more inferior there is medial raphe

Question 41

Increase of serotonin via

Answer 41

1. MAO-blockers (prevents the breakdown).
2. Reuptake Blockers :
   SSRI (Fluoxetine) - selective serotonin reuptake inhibitor.
   Cocaine
3. Reuptake reversal
   MDMA (extasy) : already re-uptaken serotonin is put back into the synaptic cleft
   - 5HT-R(serotonin) agonist ;
   LSD, mescaline, psilocybin (I don’t think this is important).

Question 42

Serotonin Synthesis :

Answer 42

• You have to have Trytophan in your diet because the brain doesn’t produce it.
• Tryptophan is transferred into serotonin by ‘tryptophan-5-hydroxylase’ ‘
  When you want to stain cells for serotonin ; you can either stain them with serotonin itself (5HT-R) or the enzyme Trytophan-5-hydroxylase

Question 43

Serotonin Receptors

Answer 43

Serotonin has both ionotropic and metabotropic receptors.

Question 44

Functions of Serotonin :

Answer 44

• Modulation of basic psychological functions such as ; mood, appetite, sleep, sexuality.
• Implicated in depression (most antidepressants block serotonin reuptake (5-HT) reuptake)
• Implicated in aggression (high serotonin levels).
• Stimulates vomiting. (not important)

Question 45

Antidepressants

Answer 45

-MAO inhibitors ;
Inhibit break down of all monoamines.
- Tricyclic antidepressants :
Inhibit reuptake of serotonin and noradrenaline.
- Selective serotonin reuptake inhibitors (SSRIs) :
- Inhibit the reuptake of only serotonin.
-Compared to tricyclic which inhibits the reuptake of both serotonin and noradrenaline, SSRI have fewer side-effects.