The Synapse PDF

8/7/24 The Synapse PSYU2236/PSYX2236 Biopsychology & Learning Lecturer: Dr Patrick Nalepka (he/him) 1 Outline 1. The Neuron Revision...

8/7/24 The Synapse PSYU2236/PSYX2236 Biopsychology & Learning Lecturer: Dr Patrick Nalepka (he/him) 1 Outline 1. The Neuron Revision 2. The Synapse 2 1  8/7/24 1. The Neuron Revision B C A D C om plete th e quiz!: https://form s.office.com /r/E 4m E 885kF6 3 1. The Neuron Revision Bonus m aterial: h o w do th e voltage-gated Na + and K + channels look like? Voltage Gated Na + Channel Voltage Gated Na + Channel: Activation Cycle o f Voltage Gated Sodium Channels: Closed, Open, and Inactivated (youtube.com) Voltage Gated K + Channel: Activation Cycle o f Voltage Gated Potassium Channels (youtube.com) 4 2  8/7/24 Post Synaptic Potentials COMMUNICATION IN THE BRAIN Dendrites Presynaptic Terminals Neuron 1 Axon hillock Axon Neuron 2 Depolarisation Hyperpolarisation -65mV -80mV Neuron 3 -80mV -95mV 1. Excitatory Post Synaptic Potential (EPSP) 2. Inhibitory Post Synaptic Potential (IPSP) 3. The summed potential change results in depolarization, resulting in an Action Potential 5 5 Post Synaptic Potentials COMMUNICATION IN THE BRAIN Excitatory Post Synaptic Potential (EPSP) Communication with dendrites from other neurons can bring positive ions into the cell Positive ions produce a small depolarisation - an Excitatory Post Synaptic Potential Small EPSPs are not enough to produce an action potential Inhibitory Post Synaptic Potential (IPSP) Communication with dendrites from other neurons can bring negative ions into the cell Negative ions produce a small hyperpolarisation - an Inhibitory Post Synaptic Potential IPSPs will not produce an action potential (pushes potential down) 6 6 3  8/7/24 Postsynaptic neurons receive multiple inputs COMMUNICATION IN THE BRAIN IPSP and EPSP can cancel each other out A small depolarisation (EPSP) will cancel the effect of a small hyperpolarisation (IPSP) Sufficient EPSP will produce an action potential Once positive charge at axon hillock reaches threshold, Na+ channels are opened, positive ions flood the intracellular space and an action potential is generated. Sufficient IPSP will inhibit action potentials Large IPSPs are due to many negative ions entering the cell. The integration of charge at the axon hillock can’t reach the excitation threshold. An action potential cannot occur. NEURAL INTEGRATION 7 7 Neural Integration: Temporal and Spatial COMMUNICATION IN THE BRAIN Figure 2.3, Kalat Figure 2.4, Kalat 8 8 4  8/7/24 Neural Integration: Summary COMMUNICATION IN THE BRAIN Dendrites (mostly) receive information from different transmitters at the same time ― polarity of these dendrites may differ ― Excitatory Post Synaptic Potentials (EPSPs) increase the likelihood of generating an action potential by elevating the mV at the axon hillock ― Inhibitory Post Synaptic Potentials (IPSPs) reduce the likelihood of generating an action potential by lowering the mV at the axon hillock All of these ‘polarities’ produced by chemical transmission are integrated at the axon hillock Neural integration is the sum of the EPSP and IPSPs where increases in mV above the excitability threshold will result in an action potential Depolarisation of the neuron will occur - action potential 9 9 An aside… Neurons behave n o n - linearly – as you increase th e input, there is n o t an equal increase in th e response A rtificial neural n e tw o rks m ake use o f th is p ro p e rty in biological neural systems. from keras_classification.ipynb - Colab (google.com) We w ill discuss m ore in Tutorial 4! 10 5  8/7/24 Questions Questions? 11 2. Synaptic Transmission A critical change in the membrane potential triggers an action potential. But what causes the change in the membrane potential? 12 6  8/7/24 Sherrington and the Reflex Arc Sherrington introduced th e te r m synapse follow ing th e observation t h a t reflexes are slow er than electrical co n d u ctio n along the axon. The co m m u n ica tio n b e t w e e n neurons m u s t be th e source o f delay. From File:Prof. Charles Scott Sherrington.jpg - Wikimedia O ther observations: Commons Several weak s tim u li presented a t nearby places or tim e produce a stronger reflex (i.e., EPSPs and IPSPs) When one set o f m uscles becom e excited, a d iffe re n t set becom es relaxed (inhibitory From Nervous Systems | Organismal Biology (gatech.edu) synapses) 13 13 Where do these “inputs” come from? COMMUNICATION IN THE BRAIN How do cells talk to each other? Electrical communications: gap junctions (electrical synapses) Chemical communications: synaptic cleft (chemical synapses) 14 14 7  8/7/24 Gap Junction: Electrical Synapses COMMUNICATION IN THE BRAIN Instead of using chemical messengers they transfer ions between the plasma wall of neurites via connexons ICF The junction is specialised so that it is only a Plasma membrane small distance (3.5 nm) between cells (usually around 20 nm gap) ECF Faster communication than chemical synapse. Plasma membrane Allows two neurons to act as if they were one. Observed in instances that require synchrony ICF between neurons. e.g., coordination of left vs. right side in breathing. e.g., defensive reflexes involved in rapid escape. 15 15 Synaptic Transmission: 2-Minute Neuroscience 2-Minute Neuroscience: Synaptic Transmission (youtube.com) Do you have a resource that helped you in your revision of ‘the synapse’? Share it on Teams! 16 Patrick Nalepka: The Synapse Revision - Post your favourite resources for revision! 16 8  8/7/24 Chemical Synapses COMMUNICATION IN THE BRAIN Chemical synapses are typically formed between an axon Neurotransmitters terminal (button/bouton) and a dendritic spine They use neurotransmitters to convey messages What happens when the action potential reaches the Presynaptic presynaptic bouton? 1. Increase in calcium in axon terminal 2. Vesicles (containing neurotransmitters) are moved to the membrane and dock Vesicles 3. Once docked, vesicle content is emptied into synapse (exocytosis) Postsynaptic What happens after release? Neurotransmitters bind to receptors on postsynaptic dendrites Bouton Receptor Synaptic Cleft (20-50nm) 17 Active Zone 17 Some Possible Synaptic Arrangements COMMUNICATION IN THE BRAIN Axodendritic Axosomatic Axoaxonic 18 18 9  8/7/24 Revision: Neuron Structure Axon Hillock Axon Collaterals Axon Axon Terminal Terminal Arbor Terminal Boutons (forms synapses with other cells) 19 Exocytosis COMMUNICATION IN THE BRAIN The action potential increases [Ca2+] in the terminal bouton Vesicles are moved to the membrane by trafficking proteins (SNARE) Once docked, exocytosis occurs to empty vesicle contents into synapse vesicle terminal synapse V SNARE (vesicle) T SNARE (target) Binds to receptor neurotransmitter 20 20 10  8/7/24 Endocytosis COMMUNICATION IN THE BRAIN After binding to receptors, some neurotransmitters are recycled Vesicular Transporter terminal Transporter reuptake V SNARE (vesicle) synapse Receptor T SNARE (target) neurotransmitter Dendrite 21 21 Neurotransmitter Metabolism COMMUNICATION IN THE BRAIN Other neurotransmitters are metabolised. Once metabolised they are no longer active neurotransmitters Metabolism can occur presynaptically or in the synapse Inactive molecule Enzyme terminal Transporter reuptake Enzyme synapse Receptor Dendrite 22 22 11  8/7/24 Summary COMMUNICATION IN THE BRAIN Neurotransmitter is released upon action potential by exocytosis Neurotransmitters may then bind to the receptor to produce a biological effect Once unbound the neurotransmitters are cleared from the synapse by endocytosis through the use of transporters in the cell membrane When they have been returned to the presynaptic terminal they either undergo metabolism through a reaction with an enzyme or they are repackaged into the neurotransmitter vesicle (recycled). 23 23 Break Break Time 24 12  8/7/24 Events at the synapse COMMUNICATION IN THE BRAIN 25 25 Presynaptic axon terminal COMMUNICATION IN THE BRAIN Neurotransmitter synthesis Synaptic vesicle transporters Reuptake transporters Enzymes to metabolise neurotransmitters 26 26 13  8/7/24 The key take-away here is that Inotropic receptors; neurotransmitters that have an e ect on channels that allow ions to go in and out. (Neurotransmitters binding to ion channels which then open and close to allow sodium to rush in). It's reliant on neurotransmitters nding these receptors and then opening them on a channel by channel basis. Postsynaptic density COMMUNICATION IN THE BRAIN Receptors Neurotransmitters communicate with post synaptic neurons via receptors Receptors can connect to: 1. Ion channels (ionotropic receptors) 2. G-proteins (G-protein coupled receptors; or metabotropic receptors) 3. G-protein coupled ion channels Neurotransmitters can exert either inotropic or metabotropic effects when attached to a receptor. Inotropic effects are fast (< 1 ms) but brief (~ 5 ms half-life). Metabotropic effects are slower (~ 30 ms) but longer (> 1 s). Study of receptors systems is called Neuropharmacology 27 27 Metabotropic receptors are di erent. A NT will bind to a receptor and that receptor will activate a second messenger. So the NT is the rst messenger. The second messenger takes that info then alters the metabolic processes of that neuron (changes which genes are expressed, changes how calcium is stored in the cell) etc. The second messengers are called G-proteins. The GPs detach and deliver that message. Ionotropic Receptors COMMUNICATION IN THE BRAIN Ligand (i.e. neurotransmitter) gated ion channels Composed of subunits (α, β, γ, δ) Usually 5 subunits for each receptor Binding of neurotransmitter to subunit causes subunits to move to create a channel Binding of ACh or Glu lets positive ions into cell (Na+, Ca2): Stimulatory Binding of GABA lets negative ions into cell (Cl-): Inhibitory + positively charged - negatively charged 28 ACh = acetylcholine; Glu = Glutamate; GABA = gamma-aminobutyric 28 Why are they called subunits? 14  8/7/24 Metabotropic Receptors COMMUNICATION IN THE BRAIN When neurotransmitters (e.g., dopamine, norepinephrine, serotonin) attach to a metabotropic receptor, it initiates a sequence of metabolic reactions. Activated metabotropic receptors release GTP-binding proteins (G-proteins), a protein that carries guanosine triphosphate (GTP – an energy-storing molecule). G-proteins can either activate ion channels or increase the concentration of second messengers which communicates to different areas of the cell. Figure 2.16, Kalat, 13th Ed. 29 29 Metabotropic Receptors COMMUNICATION IN THE BRAIN Metabotropic Receptor features: Single polypeptide: 7 membrane spanning domains Each is an alpha (α) helix where neurotransmitter can bind G-protein coupled receptors (GPCR) Neurotransmitters bind to the α-helices. Instead of directly opening ion channels, the receptor couples/binds to a G-protein G-proteins have three subunits (α, β and γ). Receptor structure changes when the receptor binds to it 30 30 15  8/7/24 Metabotropic Receptors & G-protein COMMUNICATION IN THE BRAIN 31 31 Binding Activates the G-Protein COMMUNICATION IN THE BRAIN 32 32 16  8/7/24 In this example here speci c proteins which then have e ects on the cell such as controlling how much calcium is stored in the cell, what genes are expressed. The G-proteins could also open up some ion channels as well if they wanted to. The activated G-Protein splits COMMUNICATION IN THE BRAIN 33 33 These slides are for people who really want to know, its kinda outside the scope of this class but there are other resources available online if you also want to know. G-Protein subunits bind to other proteins COMMUNICATION IN THE BRAIN 34 34 17  8/7/24 G-Protein subunits bind to other proteins COMMUNICATION IN THE BRAIN 35 35 G-Proteins can also bind ion channels COMMUNICATION IN THE BRAIN 36 36 18  8/7/24 The membrane returns to ‘normal’ COMMUNICATION IN THE BRAIN 37 37 The key take away here concerning these metabotropic receptors and g-proteins is that they're able to amplify the e ects of neurotransmitters. So for inotropic receptors they behave locally to a speci c ion gated channel (they're able to open or close it) they're able to open sodium or chlorine to come in. Whereas metabotropic receptors they just need to receive one message from one receptor and then that protein can go o and amplify that signal to change a cascade of processes in that neuron. Second messenger systems COMMUNICATION IN THE BRAIN Many different second messenger systems Activation of enzymes important for neuronal function Cascades - allow regulation of systems with the neuron to respond to information that the neuron has received from outside transmitters. Activation of one receptor can lead α GTP to the activation of several downstream mechanisms, amplifying output e.g., Release of Calcium from stores in the cell Ca 2+ Ca 2+ Ca 2+ Ca 2+ Ca 2+ Ca2+ 38 38 19  8/7/24 Ionotropic vs Metabotropic receptors COMMUNICATION IN THE BRAIN Ionotropic receptors Fast acting Can be inefficient: one ion channel does one thing Metabotropic receptors G-protein coupled receptors linked to second messenger system are slow More sophisticated transfer of information: many systems integrated One receptor can trigger many downstream effects Slow but efficient 39 39 Inhibitory G-Proteins COMMUNICATION IN THE BRAIN Stimulatory/excitatory G-proteins (Gs or Gq) activate second messenger cascades Many receptors are linked to inhibitory G-proteins which prevent the second messenger cascades (Gi proteins) 40 40 20  8/7/24 What does this mean for the neuron? COMMUNICATION IN THE BRAIN At any one time, a neuron may receive outside information from several different neurotransmitters (NT) 41 41 What does this mean for the neuron? NEUROPHARMACOLOGY One NT may bind an ionotropic receptor and activate a sodium (Na +) channel è Sodium comes into the dendrite 42 42 21  8/7/24 What does this mean for the neuron? COMMUNICATION IN THE BRAIN G-Proteins and effector proteins are always present on the postsynaptic membrane 43 43 What does this mean for the neuron? COMMUNICATION IN THE BRAIN The same neurotransmitter may also activate a metabotropic receptor coupled to a G-protein. è GTP binds to the α subunit 44 44 22  8/7/24 What does this mean for the neuron? COMMUNICATION IN THE BRAIN The G-protein splits and the α subunit activates an effector protein è second messenger cascade 45 45 What does this mean for the neuron? NEUROPHARMACOLOGY A second neurotransmitter may bind to another G-protein coupled receptor, this time an inhibitory (Gi) protein 46 46 23  8/7/24 What does this mean for the neuron? COMMUNICATION IN THE BRAIN The α subunit of the Gi protein binds to the effector protein and inhibits its activity è Second messengers aren’t activated 47 47 What does this mean for the neuron? COMMUNICATION IN THE BRAIN The overall polarity for this part of the dendrite is POSITIVE: Excitatory Postsynaptic Potential 48 48 24  8/7/24 Receptor Feedback COMMUNICATION IN THE BRAIN Receptors are also located PRE-synaptically (autoreceptors) 49 49 Receptor Feedback COMMUNICATION IN THE BRAIN 50 50 25  8/7/24 Inhibitory G-Proteins COMMUNICATION IN THE BRAIN 51 51 Receptor Pharmacology COMMUNICATION IN THE BRAIN Receptor Pharmacology Neurons use neurotransmitters & receptors to communicate Released neurotransmitters bind to receptors Drugs can also alter neuron communication directly: A receptor agonist binds to a receptor and has an effect on the neuron A receptor antagonist binds to a receptor but does not have an effect on the neuron Stops the neurotransmitter from having an effect 52 52 26  8/7/24 Summary COMMUNICATION IN THE BRAIN 1. Neurotransmitters communicate with the post synaptic cell via receptors 2. Receptors can be connected to ― ion channels (ionotropic receptors) ― G-proteins (G-protein coupled receptors) ― G-protein coupled ion channels 3. Binding of neurotransmitter to these receptors produces a biological effect which is either excitatory or inhibitory to the cell or cell system 4. Agonists bind to the receptor to have the same effect as the neurotransmitter 5. Antagonists bind to the receptor to block the effect of the neurotransmitter 53 53 Synaptic Receptors: 2-Minute Neuroscience 2-Minute Neuroscience: Receptors & Ligands (youtube.com) Do you have a resource that helped you in your revision of ‘the synapse’? Share it on Teams! 54 Patrick Nalepka: The Synapse Revision - Post your favourite resources for revision! 54 27  8/7/24 Revision When revising Week 02 (The Neuron) and Week 03 (The Synapse), I re co m m e n d drawing: The co m p o n e n ts o f th e p r e - synaptic and p o s t - synaptic neuron. The co m p o n e n ts t h a t enable th e ‘action potential’ The co m p o n e n ts t h a t enable ‘synaptic transmission’ Modifying each o f these co m p o n e n ts (e.g., increasing th e ir num ber, rem oving/blocking com ponents) and w h a t w o u ld t h a t m ean fo r neuronal com m unication. For exam ple like this: Synaptic transmission I The Synapse I How Neurons Communicate – YouTube Do you have a resource that helped you in your revision of ‘the synapse’? Share it on Teams! Patrick Nalepka: The Synapse Revision - Post your favourite resources for revision! 55 Next Time The le ctu re to p ic next w eek is “Neuroanatom y” Lecturer: Dr Christina Perry Reading: The Kalat chapter t it le d “A natom y and Research M ethods” Tutorial 1 continues th is w eek fo r s tu d e n ts enrolled in Stream B classes. In - person: Arrive t o your class on tim e! (12SW Room 317) Online: Visit your class’s te a m channel on tim e! OUA: OUA s tu d e n ts can view Tutorial 1 on iLearn. Make use o f our PSYUX2236-2 0 2 4 -S2 Team fo r u n it discussions, ask questions, or help answer questions f r o m your peers! Have a good day! 56 28