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Case 20: Neurophysiology (Neurotransmission) 1 - Coggle Diagram
Case 20: Neurophysiology (Neurotransmission) 1
Serotonin
List the Projection Sites of the Serotonin
Serotonin is released by the Raphe Nuclei found in the Dorsal Raphe
Serotonin is also known as 5-Hydroxytryptamine (5-HT)
Serotonin Projections include:
Amygdala
Basal Forebrain
Hypothalamus
Thalamus
Hippocampus
Cerebral Cortex
Functions of Serotonin
Outline the Functions of Serotonin
Serotonin is responsible for:
Mood, Emotional behaviour and Sleep
Ant-depressants elevate synaptic serotonin levels
Control of food intake
Ant-depressants lead to the loss of appetite
Pain
Serotonin Receptors in the spinal cord inhibit pain pathways
Complex Cognitive Pathways
Thermoregulation
NOTE: Serotonin does not cross the BBB
Synthesis of Serotonin
Describe the Synthesis of Serotonin
Serotonin is synthesised from Tryptophan, found in the ECF
Serotonin CANNOT cross the Blood Brain Barrier, therefore Neurons produce their own Serotonin
Synthesis of Serotonin is as follows:
Serotonin is synthesises by the action of Tryptophan Hydroxylase
Tryptophan hydroxylase converts Tryptophan (amino acid) into 5-Hydroxytryptophan (5-HTP)
5-Hydroxytryptophan (5-HTP) undergoes decarboxylation in the presence of 5-Hydroxytryptophan decarboxylase (5-HTP decarboxylase) to produce 5-Hydroxytryptamine (5-HT)
5-Hydroxytryptamine is known as Serotonin
Serotonin is then metabolised by the Monoamine Oxidase (MOA) into the corresponding inactive amino acid
Lifecycle of Serotonin after being release into the Synapse
Outline the Lifecyle of Serotonin after being release into the Synapse
After being relapsed into the
Serotonin is removed from the Synapse by transporter (SERT)
Once in the pre-synaptic terminal, Serotonin is either:
Reloaded into the Synaptic Vesicles
OR
It is broken down by the Monoamine Oxidase (MAO) enzyme into an inactive amino acid
Serotonin Receptors
Serotonin has many effects due to its wide variety of Serotonin Receptors
Serotonin Drug Alterations
Many different classes of drugs interact with the Serotonergic System
List the Classes of Drugs which interact with Serotonin
There are 4 classes of drugs which interact with Serotonin:
Anti-depressants
Psychedelics
Antiemetic
Anti-Migraine Drugs
Outline the Classes of Drugs which interact with Serotonin
There are 4 classes of drugs which interact with Serotonin:
Anti-Depressants
Anti-Depressants elevate the level of Serotonin in the synapse by:
Blocking the transporter for re-uptake
Blocking the Catabolic Enzyme known as Monoamine Oxidase (MAO)
Psychedelics
Psychedelics are agonists of Serotonin Receptors
Psychedelics cause hallucination
Antiemetics
Antiemetics are antagonists of Serotonin Receptors in the Gut and in the Brain
Antiemetics block nausea and vomiting
Anti-Migraine Drugs
Anti-Migraine Drugs are agonists of Serotonin Receptors
Anti-Migraine Drugs cause pain modulation
Catecholamines
List the names of the types of Catecholamines
There are three Catecholamines:
Dopamine
Epinephrine
Norepinephrine
Functions of Catecholamines
Outline the Functions of Catecholamines
Catecholamines are responsible for the control of:
Mood
Movement
Attention and Autonomic Functions
Lifecycle of Catecholamines
Describe the Lifecycle of Catecholamines
Actions of the Catecholamines terminate due to the selective re-uptake of Catecholamines back into the Pre-Synaptic Terminal by Sodium-dependent (Na+) transporters
This is often where drugs act to prove various effects
In the presynaptic terminal, Catecholamines are either:
Reloaded into the Synaptic Vesicle
OR
catecholamines are metabolised by the Catabolic Enzyme known as Monoamine Oxidase (MAO) found on the outer membrane mitochondria
Catecholamine Synthesis
Describe the Synthesis of Catecholamines
Catecholamines are synthesised from Tyrosine
Tyrosine hydrolase is a rate-limiting enzyme involved in the synthesis of Catecholamines
Synthesis of Catecholamines is as follows:
Tyrosine is converted into L-Dopa by the action of the Tyrosine Hydroxylase enzyme
L-Dopa undergoes Decarboxylation in the presence of Dopa Decarboxylase, in order to produce Dopamine
Dopamine can be hydroxylated into Norepinephrine
Norepinephrine can be further processed into Epinephrine
Projections of Dopamine
List the Projection Pathways of Dopamine
Dopamine is involved in 4 Projection Pathways:
Nigrostriatal Pathway
Mesolimbic Pathways
Mesocortical Pathway
Tuberoinfundibular Pathway
Nigrostriatal Pathway
Describe the Nigrostriatal Pathway according to Origin, Projection, Function and Disease
Origin:
Substantia nigra of the midbrain
Projection:
Striatum
Function:
Movements
Disorders:
Parkinson's Disease
Other diseases of movement
Mesolimbic Pathway
Describe the Mesolimbic Pathway Origin, Projection, Function and Disease
Origin: Ventral Tegmental Area
Projection: Limbic System
Nucleus accumbens
Amygdala
Hippocampus
Function: Motivation and Desire
Disease:
Addiction
Schizophrenia
Depression
ADHD
Mesocortical Pathway
Describe the Mesocortical Pathway according to Origin, Projection, Function, and Diseases
Origin: Ventral Tegmental Area
Projection: Cortex of the Frontal Lobe
Function:
Motivation in cognition
Motivation in sensation
Conscious emotion
Diseases:
Schizophrenia
ADHD
Tuberoinfundibular Pathway
Describe the Tuberoinfundibular Pathway according to Origin, Projection, and Function
Origin: Arcuate Nucleus of the Hypothalamus
Projection: Posterior Lobe of the Pituitary Gland
Function: Regulation of Prolactin release
Dopamine Lifecycle
Explain the Lifecycle of Dopamine after it is released into the Synaptic Cleft
After Dopamine has been released, Dopamine binds to the G-protein receptor on the post-synaptic neuron
Thereafter, Dopamine is transported back into the Pre-synaptic Terminal
At the Pre-synaptic Terminal, the Dopamine is either:
Reloaded back into the Synaptic Vesicle
OR
Dopamine is metabolised by the Catabolic Enzyme, known as Monoamine Oxidase (MAO)
List the Functions of the Auto-Receptor for Dopamine
Auto-Receptor for Dopamine gives feedback to Pre-Synaptic Neuron about what is happening in the synapse
Auto-Receptor for Dopamine regulates the release or re-uptake of Dopamine
Dopamine Receptors
Dopamine as a neurotransmitter can excitatory or inhibitory depending o the type of receptor it binds to
List the types of Dopamine Receptors
There are 5 types of Dopamine Receptors:
D1
D2
D3
D4
D5
D1 and D5 Dopamine Receptors are are excitatory receptors
They are responsible for the activation of Adenylate cyclase
D2, D3, D4 Dopamine Receptors are inhibitory receptors
They are responsible for the inhibition of Adenylate cyclase
Disorders of Dopamine
List the Disorders of Dopamine
Anhedonia (Depression)
Parkinson's Disease
ADHD
Schizophrenia
Alterations of Dopamine
List the Drugs Alteration of Dopamine
Dopamine has alterations with the following drugs:
Cocaine
Methamphetamine
Outline the Drug Alterations of Dopamine
Cocaine blocks the re-uptake of Dopamine from the Synaptic Cleft
Cocaine does this by blocking the transporter on the Pre-Synaptic Neuron
As a result, there is an increase in the Dopamine Levels in the synaptic cleft
As a result, Dopamine binds to the Dopamine receptors over and over again, thus overstimulating the cell
Methamphetamine reverses the action of the Dopamine Transporter
Instead of transporting Dopamine back into the Pre-synaptic Neuron
The Dopamine Transporter actively pumps out more Dopamine out of the cell into the Synapse
NOTE: Anything that messes with the Dopamine system will be addictive
Norepinephrine
Outline the Projections sites, and Function of Norepinephrine
Norepinephrine is released by the:
Lateral Tegmental Area (Pons/Medulla Oblongata)
Locus Coeruleus of the Pons
Norepinephrine projection sites are as follows:
Neocortex
Amygdala
Hippocampus
Thalamus
Hypothalamus
Cerebellum
Norepinephrine has the following functions:
Vigilance
Arousal
Synthesis of Norepinephrine
Describe the Synthesis of Norepinephrine
Dopamine Beta-Hydroxylase converts Dopamine into Norepinephrine
Enzyme that converts Dopamine to Norepinephrine is not present in the Cytosol
Enzyme is found in the synaptic vesicles
Therefore, Dopamine is taken back into the synaptic vesicles by the Dopamine transporter protein
Dopamine in the synaptic vesicles is then converted into Norepinephrine by Dopamine Beta-hydroxylase
Norepinephrine is then released into synaptic cleft by exocytosis
Norepinephrine then binds to the Post-synaptic Adrenergic Receptor and later removal
Factors Which Affect the Removal of Norepinephrine
Explain the Factors Which Affect the Removal of Norepinephrine
Factors which affect the removal of Norepinephrine is Auto-Inhibition
Activation of the Pre-synaptic adrenergic receptors results in the inhibition of the release of Epinephrine
This is known as Auto-Inhibition
Auto-Inhibition is different from the Negative Feedback Pathway in which the Synthesis of Norepinephrine is blocked at its rate limiting step
Rate Limiting Step is the Conversion of Tyrosine into L-Dopa in the presence of Tyrosine Hydroxylase
Lifecycle of Norepinephrine
Describe the Lifecycle of Norepinephrine after release into the Synaptic Cleft
After the release of Norepinephrine into the Synaptic Cleft, Norepinephrine is taken back into the Pre-Synaptic Terminal
Norepinephrine re-uptake is done by the transport protein known as Neuronal Norepinephrine Re-uptake Transporter (NET)
Norepinephrine Re-uptake Transporter (NET) is a secondary active transport
Norepinephrine Reuptake Transporter (NET)) is dependent on the uptake of Na+ (Sodium) and Cl- (Chloride)
Once in the Pre-Synaptic Terminal, Norepinephrine is either:
Reloaded into the Synaptic Vesicle by the Vesicular Monoamine Transporter-2
OR
Norepinephrine is metabolised by a Catabolic Enzyme known as Monoamine Oxidase (MAO)
Alterations of Norepinephrine
Norepinephrine has alterations with Diseases and Drugs
List and Outline the Disease and Drug Alterations of Norepinephrine
Disease Alterations for Norepinephrine include:
Depression
ADHD
Depression causes apathy
ADHD causes a reduced focus
Drugs Alterations for Norepinephrine include:
Cocaine
Methamphetamine
Amphetamines
Methylphenidate
Anti-depressants
Anti-Depressants elevate the levels of Norepinephrine in the Synaptic Cleft by:
Blocking the Norepinephrine Re-Uptake Transporter
Blocking the MAO Enzyme which metabolises Norepinephrine
Reversing the function of the Norepinephrine Re-Uptake Transporter
Causing the Norepinephrine Re-Uptake Transporter to pump more Norepinephrine into the Synaptic Cleft
Epinephrine
Outline the Projections and Function of Epinephrine
Epinephrine is secreted by the Chromaffin Cells of the Adrenal medulla and a small number of Neurons in the Medulla Oblongata
Epinephrine plays an important role in fight-or-flight response by
Increasing blood flow to muscles
Increasing cardiac output by acting on the SA Node
Pupil dilation response
Blood Sugar level
Synthesis of Epinephrine
Explain the Synthesis of Epinephrine
Prior to the synthesis of Epinephrine , Norepinephrine is released from the Synaptic Vesicle into the Cytosol
Epinephrine is synthesised from Norepinephrine by the process of Transmethylation
This reaction is catalyzed by the enzyme PNMT (Phentolamine-N-Methyl Transferase)
And requires SAM as a Methyl donor
Phentolamine-N-Methyl Transferase(PNMT) enzyme is found in the Adrenal Medulla
Receptors for Norepinephrine and Epinephrine
List the Receptors for Norepinephrine and Epinephrine
Norepinephrine and Epinephrine bind to Adrenergic Receptors
Adrenergic Receptors are divided into Alpha and/or Beta Adrenergic Receptors
Beta-2 Receptors are found on:
Smooth muscle and cause relaxation
Adipose tissue and cease Lipolysis
Non-pregnant uterus and cause relaxation
Alterations of Disease with Epinephrine
Hypothalamus stimulates the pituitary gland to stimulate the adrenal medulla to release Epinephrine
Diseases such as the following can lead to an overproduction or underproduction of Epinephrine:
Tumour in the Hypothalamus
Tumour in the Pituitary gland
Tumour in the Adrenal gland
Increased Levels of Epinephrine cause the following symptoms;
Sweating
Tachycardia and Tachypnoea
Anxiety
Transient, episodic hypertension
Headaches
Palpitations
Decreased levels of Epinephrine can cause the following symptoms:
Dizziness
Changes in vision
Loss of fight-or-flight response
