Neurotransmission PDF

Neurotransmitters LG1) What are neurotransmitters and how do they work? ð Chemical messengers that facilitate communication between neurons and others cells ( such as muscle cells or gland cells) at synapses ð Synaptic transmission: The role of Neurotransmission ·...

Neurotransmitters LG1) What are neurotransmitters and how do they work? ð Chemical messengers that facilitate communication between neurons and others cells ( such as muscle cells or gland cells) at synapses ð Synaptic transmission: The role of Neurotransmission · Synapses: Specialized junctions where neurons communicate with each other or with other cell types Synaptic vesicles: small, spherical(kugelförmig) structures located within the presynaptic axon terminal, which contain neurotransmitter molecules Presynaptic Membrane: specialized membrane of the axon terminal of the transmitting neuron > Voltage-Gated Calcium Channels > Specialized proteins for vesicle fusion (i.e. SNARE) – they mediate the docking and fusion Synaptic Cleft: A narrow gap that separates the presynaptic and postsynaptic neurons Postsynaptic Membrane: specialized membrane on the receiving neuron´s dendrite or cell body > Populated with receptors Receptors: specialized protein molecules embedded in the postsynaptic membrane, which bind to specific neurotransmitter molecules a) What is the di8erence between various types of neurotransmitters? Amino Acid Neurotransmitters: fundamental building blocks of protein o Glutamate: most widespread neurotransmitter, primary excitatory neurotransmitter in the central nervouse system -> playing crucial roles in learning, memory and synaptic plasticity too much can be toxic and cause cell death ( stroke, epilepsy,Alzheimer, parkinsons) - NMDA receptor and AMPA receptors o Gamma-aminobutyric acid (GABA) : second most widespread neurotransmitter main inhibitory (hemmend) neurotransmitter counterbalancing glutamate´s excitatory actions and contributing to the regulation of neural activity and the prevention of overexcitation too little can lead to seizure too much increase in heart rate, emotional recation, blood pressure  o Aspartate: excitatory neurotransmitter, often working alongside glutamate o Glycine: inhibitory neurotransmitter, particularly in the spinal cord and brainstem Biogenic Amines/Monoamines: 1) Catecholamines: neurotransmitters share catechol ring structure and are synthesised from the amino acid tyrosine § Dopamine: five diSerent types labelled from D1 to D5 plays role in reward, motivation, motor control, arousal, cognition § Norepinephrine: involved in arousal, attention, mood regulation and “fight-or-flight” response § Epinephrine (adrenaline): produced in the adrenal glands (located in kidney) and acts as a hormone, but also functions as a neurotransmitter, contributing to stress responses 2) Indoleamines: synthesized from the amino acid tryptophan § Serotonin: diverse roles in regulating mood, sleep, cognition, appetite, behavior, temperature § Melatonin: regulates sleep-wake cycle Neuropeptides: can be categorized in 5 subgroups a) Tachykins (brain-gut peptides) b) Neurohypophyseal hormones c) Hypothalamic releasing horones d) Opioid peptides: includes endorphins and enkephalins e) Other neuropeptides: insuline, secretins (e.g. glucagon) Acetylcholine (ACh): in its own bio-chemical group Excitatory as well as inhibitory eSect depending on receptor Nicotine binds to Nicotinic acetylcholine receptors to increase arousal, enhancing learning/memory 1. What is the process of neurotransmission? 1. Arrival of the action potential – this depolarizes the presynaptic membrane 2. Calcium Influx: The depolarization opens voltage-gated calcium ( Ca2+) channels. This allows an influx of Ca2+ ions into the axon terminal 3. Vesicle fusion with presynaptic membrane: The influx of Ca2+ ions triggers synaptic vesicles to fuse with the presynaptic membrane – Fusion is mediated(vermittelt) by specialized proteins like SNAREs 4. Neurotransmitter release: The neurotransmitters are released through exocytosis (process of a cell moving large material from intracellular to extracellular (inside and outside of cell) using vesicles) 5. Receptor binding: The neurotransmitter molecules bind to specific receptor proteins embedded in the postsynaptic membrane 6. Postsynaptic Potential: The binding of neurotransmitters to receptors triggers changes in the postsynaptic neuron § Opening of ion channels, resulting in either an excitatory postsynaptic potential (EPSP) => depolarizing the postsynaptic membrane OR inhibitory postsynaptic potential (IPSP) => hyperpolarizing postsynaptic membrane § Activate G protein-coupled receptors (GPCRs) initiating slower, indirect eSects on the postsynaptic membrane through second messenger systems. Second messenger can modulate various cellar processes, including the opening of other ion channels or alterations in gene expression (process by which the information encoded in a gene turned into a function) After exerting their e;ects on the postsynaptic neuron, neurotransmitters must be removed from the synaptic cleft to prevent continuous stimulation. This event can occur through several mechanisms Neurotransmitter clearance: 1. Reupatke: The presynaptic neuron reabsorbs the neurotransmitter molecules back into the axon terminal (recycling - Retrograde transport ) 2. Enzymatic Degradation: Enzymes in the synaptic cleft break down the neurotransmitter molecules (destroying) 3. DiMusion: Neurotransmitter molecules diSuse away from the synaptic cleft. Clinical significance of Neurotransmitters Drug thing LG2) What is post-synaptic potential and how does it work? ð Electrical changes in the membrane potential of the postsynaptic neuron, triggered by the binding of neurotransmitters to receptors on the postsynaptic membrane Two types 1. Excitatory Postsynaptic Potentials (EPSPs): neurotransmitter-receptor interaction opens channels that allow positively charged ions, like sodium, to flow into the postsynaptic neuron -> membrane becomes depolarized -> making the neuron more likely to fire action potential 2. Inhibitory Postsynaptic Potential (IPSPs): neurotransmitter-receptor interaction opens channels for negatively charged ions, like chloride (Cl-) to enter postsynaptic neuron OR for positevly charged ions, like Potassium, to leave -> membrane becomes hyperpolarized -> making neuron less likely to fire action potential Signal Integration: neuron receives inputs from thousands of synapses -> postsynaptic membrane integrates these numerous EPSPs and IPSPs -> combined eSect of both potentials (like a calculater) determines whether overall change in membrane potential at axon hillock reaches the threshold for triggering an action potential LG3) How does serotonin influence the neurotransmission? (focus also in terms of depression) Widespread projections: serotonin projects to various brain regions (like, limbic system, cortex, cerebellum, spinal cord) ð This enables serotonin to have influence on diverse range of functions, like sleep, mood, sexual behavior, anxiety and cognition Interacts with variety of receptor subtypes Excitatory neurotransmitter LG4) What is the role of the receptors in neurotransmission? Acting as gatekeepers that determine how neurons respond to the chemical signals they receive  Specialized protein molecules embedded in the postsynaptic membrane Recognize and bind to specific neurotransmitters released from the presynaptic neuron Two main types of recptors: 1. Ionotropic Receptors (Ligand-Gated Ion Channels): - Directly coupled ion channels è When neurotransmitter binds to ionotropic receptor, the channel opens -> allowing ions to flow across the membrane+this flow rapidly alters the membrane potential -> either EPSP or IPSP depending on the type of ion channel involved 2. Metabotropic Receptors (G Protein-Coupled Receptors): - Not directly linked to ion channels è Neurotransmitter binds to metabotropic receptor, it activates a G protein -> protein interacts with other eSector proteins, like enzymes or ion channels - Activate G protein-coupled receptors (GPCRs) initiating slower, indirect eSects on the postsynaptic membrane through second messenger systems. - Second messenger can modulate various cellar processes, including the opening of other ion channels or alterations in gene expression (process by which the information encoded in a gene turned into a function) A single neurotransmitter can often activate multiple receptor subtypes è Example: acetylcholine activates both nicotinic and muscarinic receptors Receptor plasticity: number and sensitivity of receptors can be regulated, influencing the strength of synaptic connections Key mechanism underlying learning and memory è Example: repeated activation of a synapse can lead to an increase in the number of receptors -> making the synapse more responsive to the neurotransmitter Video explains https://www.youtube.com/watch?v=_sM8KBZ9k4Q Antagonist Agonist partial-agonist inverse agonist Neurotransmission and Drugs: SSRI Drug – Selective Serotonin Reuptake Inhibitors Typically used as antidepressants