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Case 20: Neurophysiology - Coggle Diagram
Case 20: Neurophysiology
Classification of NeurotransmittersList the types of NeurotransmittersThere are four types of neurotransmitters:
- Amines (and Catecholamines)
- Peptides
- Amino Acids
- Purine
- Serotonin
- Acetylcholine
- Melatonin
- Histamine
- Dopamine
- Epinephrine
- Norepinephrine
- Oxytocin
- GABA
- Glutamate
- Glycine
- Aspartate
- ATP
- Adenosine
Neurotransmitter SystemsList the types of Neurotransmitter Systems
- There are 3 types of neurotransmitter System:
- Acetylcholine (Cholinergic System)
- Glutamate (Glutamatergic System)
- GABA (GABAergic System)
AcetylcholineOutline the characteristics of Acetylcholine
- Acetylcholine is released by:
- Motor Neurons
- Neurons in the Autonomic Nervous System
- Neurons in the Basal Forebrain which project throughout the Cerebral Cortex (Neuromodulator)
Acetylcholine: Somatic Motor NeuronsOutline the Type of Motor Neuron that releases Acetylcholine and the Receptor for Acetylcholine
- Released by:
- Acetylcholine is released by Somatic Motor Neuron
- Somatic Motor Neurons control whether the muscles contract or not
- Receptor
- Nicotinic Receptor is the Acetylcholine Receptor
- Nicotinic Receptor is located in the Striated Muscle
Explain the working of Acetylcholine and the Nicotinic Receptor in the Neuromuscular Junction
- At the Neuromuscular Junction:
- Action potential in the axon terminals stimulate the Voltage-gated Calcium Channel in the Pre-synaptic neuron
- Opening of the Voltage-gated Calcium Channel allows for an influx of extra-cellular Ca2+ ions into the Axon
- Calcium binds to Acetylcholine -containing Synaptic Vesicles in the Axon Terminal
- Synaptic Vesicles then fuse with the pre-synaptic membrane and acetylcholine is released into the Synaptic Cleft
- Two Acetylcholine molecules then bind to one-ligand gated ion channel, AKA Nicotinic Receptor
- Nicotinic Receptor Channel will then open
- Nicotinic Receptor Channel is a Cation Channel which depolarises the muscle membrane
- And results in muscle contraction
- Nicotinic Receptor Channel is permeable to both Sodium and Potassium
Excitatory Post-Synaptic Potentials (EPSPs)Define the Excitatory Post-Synaptic Potentials
- Excitatory Post-Synaptic Potentials occurs when the sodium channel opens in response to a stimulus
- For example: Nicotinic Receptor Channel
- I(Na) = g(Na) x [V-E(Na)]
- I(Na) = g(Na) x [-65-62]
- I(Na) = g(Na)(-127)
Reversal PotentialExplain the concept of the Reversal Potential
- Reversal Potential of an ion is the membrane potential at which there is no net flow of that particular ion from one side of the membrane to the other side
- A negative outwards current is the SAME as a positive inward current hence Depolarization
- Sodium has an Outward Current
- EPSPs occur when the Acetylcholine binds to the Nicotinic Receptor and stimulates the opening of the Nicotinic Receptor Channels
- Opening of the Nicotinic Receptor Channels allows for an outward flow of Na+ thus producing a Depolarization of the membrane Potential
Nicotinic ReceptorOutline the features of Nicotinic Receptors
- Nicotinic Receptors are permeable to both Na+ and K+
- Therefore, the Reversal Potential of Nicotinic Receptors is a mixture of the membrane Potential of Na+ and K+
- Reversal Potential for Acetylcholine at the Synapse is 0 mV
- E(Ach) = 0 mV or E(EPSPs) = 0mV
Acetylcholine: Autonomic Nervous System
- Acetylcholine is also released by Neurons in the Autonomic Nervous System
Outline the use of Acetylcholine in the Autonomic Nervous System
- Sympathetic innervation of the Adrenal Medulla:
- Preganglionic Neuron releases Acetylcholine
- At the Pre-ganglionic synapse Acetylcholine binds to the Nicotinic Receptor of the Adrenal Medulla
- Adrenal medulla then releases Epinephrine into the Blood
- Epinephrine targets the Adrenergic receptor in effector organs
- Sympathetics Innervation:
- Preganglionic Neuron releases Acetylcholine
- In the Pre-ganglionic synapse Acetylcholine binds to the Nicotinic Receptor Postganglionic Neurons
- Post-ganglionic Neuron Epinephrine
- Epinephrine then targets Adrenergic Receptors in effector organs
- Parasympathetic Innervation:
- Preganglionic Neuron releases Acetylcholine
- In the Pre-ganglionic synapse the Acetylcholine binds to the Nicotinic Receptor of the Post-ganglionic Neuron
- Post-ganglionic Neuron also releases Acetylcholine
- In the Post-ganglionic synapse, Acetylcholine binds to the Muscarinic Receptor in Smooth Muscles
Acetylcholine ReceptorsList the Acetylcholine Receptors
- Nicotinic Receptor
- Muscarinic Receptor
List the Antagonists and Agonists of Acetylcholine Receptors
- Antagonist: Curare
- Agonist: Nicotine
- Antagonists: Atropine
- Agonist: Muscarine
Acetylcholine LifecycleExplain the Lifecycle of Acetylcholine
- Acetylcholine is a small excitatory neurotransmitter found at various locations in the PNS and CNS and at ALL Neuromuscular Junctions
- Acetylcholine is formed by the combination of Acetic Acid and Choline in the presence of Choline Acetyltransferase (ChAT) enzyme
- Acetylcholine is then transported into the synaptic vesicle via the Acetylcholine Transporter
- Due to the influx of Ca2+ Ions, the Acetylcholine-containing Synaptic Vesicle will then fuse with the neuronal membrane
- This results in the release of Acetylcholine neurotransmitter into the Synaptic Cleft
- In the Synaptic Cleft, the Acetylcholine has a specialized enzyme called the Acetylcholinesterase (AChE)
- Acetylcholinesterase is present at ALL Cholinergic Synapses responsible for the inactivation of Acetylcholine by hydrolysis
- Acetylcholinesterase (AChE) breaks down Acetylcholine into Acetic Acid (Acetate) and Choline
- After hydrolysis, Acetic Acid quickly diffuses into the surrounding medium
- Choline gets recycled back into the pre-synaptic cell by a high affinity choline uptake (HACU) system
- Choline is then recycled by the Pre-Synaptic cell for use in the synthesis of more Acetylcholine
Acetylcholine as a NeuromodulatorOutline the features of Acetylcholine as a Neuromodulator
- Acetylcholine is also released by Neurons in the Basal Forebrain which project through the Cerebral Cortex
- Function of Acetylcholine as a neuromodulator includes:
- Arousal and wakefulness
- Aspect of leaning and memory
- Receptor
- Nicotinic and Muscarinic Receptors are the receptor for Acetylcholine
Alzheimer's DiseaseOutline the clinical features of Alzheimer's Disease
- In Alzheimer's Disease, Cholinergic Neurons in the Basal Forebrain are some of the first neurons to die
- Management of Alzheimer's Disease includes Acetylcholinesterase Inhibitors to help a bit
- This prevents the breakdown of Acetylcholine in the Cholinergic Synapse to mitigate the loss of Cholinergic Neurons
GlutamateOutline the features of Glutamate
- Glutamate is a major excitatory neurotransmitter in the brain
- Glutamate is responsible for much of the direct signal transmission between neurons
Glutamate ReceptorsList the types of Glutamate Receptors and their respective Agonists
- Glutamate Receptors are named according to their Agonists
- AMPA Receptor
- Agonist of the AMPA receptor is AMPA
- NMDA Receptor
- Agonist of the NMDA Receptor is NMDA
- Kainate Receptor
- Agonist of the Kainate Receptor is Kainate
- NOTE: Glutamate has Ionotropic and Metabotropic Receptor
Glutamate ReceptorsOutline the characteristics of Glutamate Receptors
- Glutamate Receptors and Acetylcholine Receptors are responsible for EPSPs
- Reversal Potential of AMPA Receptors and NMDA Receptors is 0 mV
- This is because both AMPA receptors and NMDA receptors are permeable to Na+ and K+
- NOTE: NMDA Receptors are permeable to Na+, K+ and Ca2+
- Most excitatory synapses have a reversal potential of 0 mV due to their permeability to BOTH Na+ and K+
NMDA ReceptorsOutline the features of NMDA Receptors
- NMDA Receptors only open at depolarized/positive potentials due to the Mg2+ Block
- At Negative Potentials such as -65 mV, the Mg+ ion will sit in the pore of the NMDA Receptor Channel and blocks the receptor
- If Glutamate is attached to the NMDA Receptor, during the Mg2+ Block nothing will happen
- At Positive Potentials such as -30 mV, the Mg2+ ions will remove from the pore
- And if the Glutamate binds and activates the receptor, Na+, K+ and Ca2+ Ions will flow through the
- NMDA Receptors are also permeable to Ca2+
- Ca2+ can activate enzymes or the 2 messengers
- NMDA Receptor is important for Learning, Memory and Long Term Potentiation (LTP)
Role of Glutamate in the activation of different Glutamate ReceptorsDifferentiate the effect of Glutamate on the different types of Glutamate Receptors
- The effect of Glutamate on the NMDA Receptor is different on the AMPA Receptor
- At Resting Membrane Potential:
- Binding of Glutamate to AMPA receptor activates the AMPA receptor and allows for the efflux of Na+ Ions
- Binding Glutamate to NMDA Receptor, where the Mg2+ Ions blocks the Pore does not activate the NMDA receptor
- At a Depolarized Potential
- Binding of Glutamate to AMPA Receptor activates the AMPA Receptor and allows for an efflux of na2+
- Binding of Glutamate to the NMDA Receptor in conduction with the removal of Mg2+ block
- Allows for the activation of the NMDA Receptor and an efflux of Na+ ions
Effects of NMDA receptor activation and Ca2+ Ion influxList the Effects of NMDA receptor activation and Ca2+ Ion influx
- NMDA Receptor activation and Ca2+ Ion influx results in the:
- Strengthening of the Synapse
- This is known as Synaptic Plasticity
- Bigger EPSPs in the future
Mechanisms of Long Term PotentiationList the Mechanisms of Long term Potentiation
- NMDA Receptors play an important role in learning, memory and Long term Potentiation
- Long Term Potentiation has 3 main mechanisms
- 3 Mechanisms of Long Term Potentiation are responsible for:
- Strengthening the synaptic connection
- Enlarging the size of the future EPSPs
- Increasing conductance at Glutamatergic Synapse
- 3 Mechanisms of Long term Potentiation are as follows:
- Insertion of AMPA receptors
- Phosphorylation of AMPA Receptors by Kinase
- Retrograde Signalling which involves the enhancement of neurotransmitter release, (increase in the probability of release)
Glutamate Metabotropic ReceptorDefine the term Glutamate Metabotropic Receptors
- In Glutamate Metabotropic Receptors, the Glutamate will bind to a Glutamate receptor
- Binding of Glutamate to the Glutamate Receptor will stimulate a 2nd messenger system
- Glutamate Metabotropic Receptors allow for a small signal to cause a big effect
Glutamate ExcitotoxicityDescribe Glutamate Excitotoxicity
- Glutamate Excitotoxicity occurs as follows:
- When there has been Cerebral Ischaemia there is a reduced uptake of oxygen into the brain
- Decreased Oxygen causes impaired energy metabolism
- Impaired energy metabolism results in a:
- Sustained Glutamate release
- Depolarized membrane potential
- Depolarization of membrane potential activates the NMDA Receptor
- Sustained release of Glutamate allows for Glutamate to bind to Glutamate Receptors
- Combined action of the Glutamate binding to Glutamate Receptor and the activation of the Glutamate Receptor allows for an Influx of Ca2+ Ions
- Influx of Ca2+ ions results in cell death
- Dead Cells will then release more Ca2+ Ions and cause a toxic cycle
GABA (Gamma Amino Butyric Acid)Outline the features of GABA
- GABA is a major inhibitory neurotransmitter in the Brain
- GABA Receptors are ligand-gated Chloride Channels
- Chloride typically moves down its electrical-chemical gradient into the cell
- This results in the Intracellular Space becoming more negative
- As a results, GABAergic Receptor are responsible for IPSPs (inhibitory Post-Synaptic Potential_
GABA Receptors
- There are two types of GABA Receptors:
- Ionotropic GABA(A) Receptors
- Metabotropic GABA(B) Receptors
GABA(A) ReceptorsDescribe the features of GABA(A) Receptors
- GABA(A) Receptors are ionotropic receptors
- GABA(A) Receptors typically lead to the influx of Chloride
- This results in the Hyperpolarization of the membrane potential (Inhibitory)
- GABA(A) Receptors are target sites for:
- Alcohol
- Benzodiazepine
- Most general anaesthetics
GABA(B) ReceptorsDescribe the features of GABA(B) Receptors
- GABA(B) Receptors are metabotropic receptors
- GABA(B) Receptors are found in the Pre-synaptic Terminals
- GABA(B) Receptors lead to second messenger cascades
- This leads to an efflux of Potassium ions and Hyperpolarization
- Exit of positive K+ Ions makes the intracellular space more negative
- GABA(B) Receptors are the target site for muscle relaxant, Baclofen