Lecture 6 - Neurotransmitters 2 Flashcards by P B

Where is dopamine synthesized (most prominent areas)?

VTA, Substantia Nigra, Midbrain Reticular Formation

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Where is serotonin synthesized?

Raphe Nuclei

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Where is noradrenaline synthesized?

Locus Coeruleus

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Where is acetylcholine synthesized?

basal forebrain (basal nucleus of Meynert, substantia innominata, medial septum, ventral and horizontal limb of the diagonal band of Broca), Penducolo-Pontine tegmental nucleus, latero-dorsal tegmental nucleus

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Neuromodulators we studied:

Dopamine
Serotonin
Acetylcholine
Norepinephrine (Noradrenaline)

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Why are the modulatory systems diffused?

They are there in the entire brain

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ADHD meds are …

Reuptake blockers of the neuromodulators –> More remain in the synaptic cleft –> more activation
-most of them are Noradrenergic

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“Self-medication” of ADHD

Smoking - nicotine activates ACh receptors

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All neuromodulators target the …

PFC

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Cathecol amines

Dopamine
Norepinephrine
epinephrine

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neostriatum

(Part of the basal ganglia) - Putamen, caudate nucleus, ventral striatum

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paleostriatum

Globus pallidus external segment
Globus pallidus internal segment

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Basal ganglia parts

Neostriatum, Paleostriatum, Substantia nigra (pars compacta, pars reticulata), subthalamic nucleus

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Globus pallidus gives

The output signal of the basal ganglia

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Which parts of the Basal Ganglia get input from the substantia nigra?

Caudate and putamen

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Where does dopamine come from (the substantia nigra)?

Pars compacta (SNc)

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Neurons projecting from SCr are …

GABAergic

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DBS for Parkinson’s disease takes place in …

Subthalamic nucleus

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In rats the caudate and the putamen are …

Not separated –> called: caudate putamen

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Caudate gets input from …

The frontal cortex (is modulated there) and SNc

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Putamen gets input from …

Frontal cortex, parietal cortex, temporal cortex and SNc

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In Parkinson’s disease …

Dopamine is lost

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How is dopamine made?

Tyrosine hydroxilase (enzime) changes Tyrosine into DOPA. DOPA is changed into dopamine by DOPA decarboxylase (In noradrenergic neurons dopamine beta-hydroxylase changes dopamine into norepinephrine.

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What neurons do you stain if you stain tyrosine hydroxylase?

Dopaminergic and noradrenergic

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Parkinson medication

L-DOPA

Why give Parkinson's patients L-DOPA instead of dopamine?

Dopamine can't pass the blood-brain barrier. DOPA passes it, dopamine can be made from that. DOPA is given together with inhibitors of the enzymes that are in the blood so it is not transformed before it passes the blood-brain barrier. The inhibitors can't pass the barrier.

Dopamine reuptake

Via DAT

Cocaine and Amphetamine

Block dopamine reuptake (enhance its effect)

2 Dopamine systems

Nigro-striatal: Modulates cortical motor control and action selection -SN Meso-cortical/limbic: reward processing, motivation, modulation of cognitive (executive control) - VTA

VTA projects to

Prefrontal cortex, NA (medial shell, lateral shell, core), ventral pallidum, amygdala

What input does the medial shell of the NA get?

Dopaminergic and GABAergic

What input does the core of the NA get?

Dopaminergic

Dopamine projection in the PFC

Prelimbic area Infralimbic area

Which part of the amygdala receives dopaminergic input?

Basolateral amygdala

All dopamine receptors are ...

Metabotropic (G-protein coupled)

2 major subgroups of dopamine receptors

D1 (excite - more cAMP) D2 (inhibit - break down cAMP)

Where are dopamine receptors?

all over the cortex: except primary auditory and visual cortex

Action selection and movement initiation is mediated by...

The cortico-striatal loop

Nigro-striatal loop

Motor cortex targets basal ganglia (dorsal striatum, also targeted by SN) -->Globus pallidus -->Thalamus --> Motor cortex

Transmitters in the nigro-striatal loop

SN: Dopamine BG:GABA Thalamus: Glutamate Cortex: Glutamate

Parkinson's symptoms

Bradykinesia/Akinesia: slowing/loss of movements (mechanism behind it: The increase of the motor threshold. You want to move but can't)

What is the dopaminergic system coming from VTA important for?

Central role in valuation of actions and stimuli Valuation is important for optimal decision making Crucial for learning values (reinforcement learning)

Dopamine is important for

Feeling rewarded

DBS of the reward system can alleviate ...

Depression (anhedonia) - MFB and connected areas are stimulated

When do you make few working memory errors?

When you have optimal D1 activity (increased and decreased amount of dopamine leads to more errors --> Inverted U shape response)

Risk factors for Parkinson's disease

Pesticides (kill your dopamine) Melanoma Infections Traumatic brain damage Milk/Yogurts

What helps to prevent PD

Vitamin E Anthocyanin (stuff in tomatoes) Green leaves Exercise Smoking

Noradrenaline projects

All over the brain

For noradrenaline to be produced which enzyme is crucial?

Dopamine beta hydroxylase

Functions of the noradrenergic systems

Arousal, mediates stress (fight or flight), neurotransmitter in the sympathetic nervous system, neuromodulator in the CNS.

Noradrenaline receptors

G-protein coupled (doesn't open channels, messes wit the intracellular signals of the Glutamate and GABA cells) -Beta receptors: in the body (in heart - beta blockers work for overexcitedness - get the arousal down) -Alpha receptors

Epipen

Noradrenaline: lungs open, heart starts to beat extra

Serotonin synthesis

Raphe nucleus

Projections of serotonergic neurons

All over the brain

Serotonin reuptake blockers

SSRIs Tryciclic antidepressants Cocaine

Serotonin reuptake reversal by

MDMA

Agonist of serotonin

LSD, mescaline, psylocibin

Where is most of our serotonin?

In our gut

What processes is serotonin involved in (in the brain)?

It is involved in mood enhancement, anxiety, arousal, circadian rhythm, eating disorders, migraine, pain, drug abuse

How is serotonin made?

Tryptophan-5-hydroxilase changes Tryptophan (you can't make it, you have to eat it e.g. chocolate) into 5-Hydroxytriptophan --> from that serotonin is made

Serotonergic receptors

Ionotropic receptor (1) Metabotropic receptors (most of them)

Most of dopamine, noradrenaline, and serotinin receptors are

Metabotropic

What mental disorder is serotonin implicated in?

Depression (most antidepressants block 5-HT reuptake)

Too much serotonin is implicated in

Aggression

MAO inhibitors

Antidepressants: Inhibit breakdown of all monoamines

Tricyclic antidepressants

Inhibit reuptake of serotonin and norepinephrine

SSRIs

inhibit reuptake of only serotonin (fewer side effect than for tricyclic antidepressants, similar efficacy)