Neurotransmitter 2 Flashcards
(45 cards)
Modulators
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.
Key names of the synthesis areas of ACh, serotonin, dopamine, noradrenaline.
ACh : Basal forebrain
Serotonin : Raphe Nuclei
Dopamine : Ventral Tegmentum
Noradrenaline : Locus Coeruleus
ADHD :
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.
Treatment for ADHD
Because you have low cortical activity in the prefrontal cortex , you can treat it via noradrenergic system, serotonergic system, cholinergic system and dopaminergic system.
Parkinsons’ Disease
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.
Dopamine Synthesis
and Noradrenaline synthesis
- Tyrosine becomes DOPA by tyrosine hydroxylase.
- DOPA becomes Dopamine by DOPA decarboxylase.
- Dopamine is transferred into noradrenaline by dopamine B-hydroxylase.
Cells that are stained with tyrosine hydroxylase
- either dopaminergic cells or noradrenergic cells.
Cells you stain for dopamine B-hydroxylase
You can be sure it is noradrenaline cells and not dopamine cells.
Dopamine Synthesis Areas :
1) Substantia Nigra (A9)
2) Ventral Tegmental Area
3) Olfactory Tubeculum
Dopamine System Projections
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.
Medial Forebrain Bundle is important for :
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.
Dopamine Reuptake
via dopamine reuptake transporters.
Cocaine and Amphetamine blocks the reuptake.
Functions of Nigra-Striatal Projections :
- From substantia nigra to striatum (caudate,putamen) and Nucleus Accumbens.
- It modulates cortical motor control and action selection.
Functions of Meso-Cortical /Limbic Projections :
From ventral tegmental area to prefrontal cortex /Amygdala-Hippocampus.
Blood-Brain Barrier and Dopamine :
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.
Dopamine Function
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’.
Dopamine Receptors :
- 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.
cAMP :
Second messenger that transfers information from G-proteins to the rest of the brain.
Nigro-Striatal System Function
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.
Nigra-Striatal System Transmitters and the pathway :
- Excitation of dorsal striatum by the cortex.
- Excitation of dorsal striatum from substantia nigra via D1 receptors. (stronger inhibition info is sent)
- Dorsal Striatum inhibits globus pallidus. (external)
- Normally globes pallidus is inhibitory of the thalamus but now it is inhibition is inhibited.
- 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.
Methylphenidate / Ritalin
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.
When you are away from your optimal dopamine content ?
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.
Where does noradrenaline synthesized ?
Where do the projections go ?
Locus Coeruleus
Projections go to all over the brain.
Reuptake of Noradrenaline (Norepinephrine)
Reuptake via Noreadrenaline Transporter (NET)
