Week 3 Lectures PDF

Week 3: Learning Outcomes By the end of Topic 1 you will be able to: - Explain how resting membrane potentials (RMP) are established Explain how neurons integrate incoming signals Understand how an action potential (AP) is generated in response to an appropriate stimu...

Week 3: Learning Outcomes By the end of Topic 1 you will be able to: - Explain how resting membrane potentials (RMP) are established Explain how neurons integrate incoming signals Understand how an action potential (AP) is generated in response to an appropriate stimulus Describe how an AP is conducted along both myelinated and unmyelinated axons Explain how a signal is transmitted to a postsynaptic cell via neurotransmitter release By the end of Topic 2 you will be able to: Give specific examples of neurotransmitters and the rate limiting enzymes for their synthesis Outline the key features and mechanisms of action of ionotropic and metabotropic receptors classes and understand how named neurotransmitters activate these receptors Recognise that drugs can change the functional availability of neurotransmitters in the brain by modifying their synthesis, storage, release, reuptake and degradation By the end of Topic 3 you will be able to: List some of the consequences of defects in neurotransmission Describe the main symptoms and risk factors for schizophrenia Outline the dopamine hypothesis of schizophrenia Appreciate the involvement of other neurotransmitters in schizophrenia, such as glutamate  08/07/2019 INSTITUTE OF PSYCHIATRY, PSYCHOLOGY & NEUROSCIENCE Module: Dr Phil Holland Biological Foundations of Mental Health Topic 1: Week 3: Action potentials and Synaptic transmission and neurotransmitter systems synaptic transmission Part 1 of 5 - Topic list This week, we will be looking at the following topics: Topic 1: Action potentials and synaptic transmission Topic 2: Neurotransmitters, receptors and pathways Topic 3: Neurotransmission defects and mental health: Focus on schizophrenia Click Next to continue Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 2 of 10 1  08/07/2019 Part 1 * Part 1 Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 3 of 10 Introduction We will study how neurons set up their resting membrane potential and how they generate and transmit potentials. Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 4 of 10 2  08/07/2019 The membrane Axon Extracellular space Neuron inname imme - Na+/K+-ATPase pump Na+ channels K+ channels - Phospholipid bilayer (lipid bilayer) mphire Leak channel Gated channel Intracellular space T Leak channel - Gated channel by closed & resting open condition Week 3 Synaptic transmission and neurotransmitter systems ↑ Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 5 of 10 Resting membrane potential: Leak channels repelled Axon Na+ sodium Extracellular space ~ K+ potassium as Cl- Cl- Cl- chloride Neuron Cl- Na+ Na+ Na+ a Na+ K+ Na+ K+ K+ K+ K+ Na+ K+ mothn K+ leak channel K+ leak channel Na+ leak channel K+ leak channel S organic anion Cl- Intracellular space organic anion Week 3 fare stint y Synaptic transmission and neurotransmitter systems oa cha Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 6 of 10 3  08/07/2019 Resting membrane potential: Na+/K+-ATPase - Axon K+ K+ Na+ sodium pumper K+ Extracellular space K+ potassium Na+ - Cl- Na+ - Na+ Cl- chloride Neuron Cl- K+ Na+ Cl- Na+ K+ Na+ Cl- Na+ Cl- Na+/K+-ATPase pump - e a Helpin K+ K+ K+ Cl- ATP K+ - K+ Na+ K+ K+ Na+ K+ Na+ K+ Cl- Na+ Na+ K+ Intracellular space Na+/K+-ATPase pump: - increases the concentration of sodium in the extracellular space The exchange of positively charged ions help to maintain the net negativity increases the concentration of potassium in the intracellular space of the intracellular space compared to the extracellular space. F Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 7 of 10 Salesoutd equilibria al- P · Resting membrane potential: Ionic forces # Axon Na+ Na+ Na+ sodium Na+ K+ Extracellular space K+ potassium Cl- K+ Na+ Na+ Cl- Cl- chloride Neuron Na+ Na+ Na+ Cl- Cl- K+ Na+ Cl- K+ Cl- Cl- K+ organic K+ K+ organic anion anion K+ K+ Na+ Na+ K+ Cl- Cl- Na+ K + K+ - K+ Na+ Intracellular space Equilibrium potential: Electrostatic force The point for any ion where the net flux across the membrane is zero, due to the force of the electrostatically charged component and the force of the diffusion being equal to each other. Force of diffusion Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 8 of 10 4  08/07/2019 Extracellular & intracellular ionic concentrations Axon Extracellular space Cl- Na+ K+ -60 to -70 mV Neuron 120mM 150mM 5mM --- ↑ Na+/K+-ATPase pump Na+ channels K+ channels relati, Cl- Na+ K+ 10mM organic 15mM 140mM Na+ sodium anion A- K+ potassium Intracellular space 100mM Cl- chloride Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 9 of 10 End of part 1 End of part 1 Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 10 of 10 5  08/07/2019 INSTITUTE OF PSYCHIATRY, PSYCHOLOGY & NEUROSCIENCE Module: Dr Phil Holland Biological Foundations of Mental Health Topic 1: Week 3: Action potentials and Synaptic transmission and neurotransmitter systems Synaptic transmission Part 2 of 5 Part 2 Part 2 Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 2 of 10 1  08/07/2019 Direction of travel from neuron to neuron - Presynaptic neuron - & Neurons can receive up to 400 presynaptic inputs. Dendrites Axon Cell body Axon initial segment (AIS) Dendrites Cell body Postsynaptic neuron - Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 3 of 10 - The graded potentials analet dupp Na+ sodium Such Potential will diminish quickly - Crapidly des Stimulus * Graded potential: Change in potential of the membrane around the ion channel, which can be positive or negative. Ligand gated channel Na+ Potassium and sodium ions are positively charged and Na+ cause a depolarisation of the postsynaptic cell. K+ Cl- Chloride ions are negatively charged and inhibit the likelihood of firing. Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 4 of 10 2  08/07/2019 Triggering an action potential -55mV Threshold value that will trigger a neurotransmitter neuron to fire an action potential release Presynaptic Postsynaptic * AIS (axon 30 initial No action potential (AP): decay of the graded segment) 0 potential activates a return of the cell to -55 - graded potential its resting -70 membrane state mV No AP as it moves through the cell body, it diminishes rapidly 30 Action potential (AP): 0 a rapid flux of sodium ions -55 - - -70 mV AP Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 5 of 10 # Spatial summation of EPSP’s Presynaptic D Spatial summation is based on the location of inputs around the 30 dendrites and the cell body. 0 -55 Postsynaptic -70 mV No AP Presynaptic # A larger graded potential travels to the axon initial segment and generates an action potential 30 AIS (axon initial segment) 0 Presynaptic -55 -70 mV AP Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 6 of 10 3  08/07/2019 Temporal summation of EPSP’s (1) Presynaptic Temporal summation is based on the timing of triggering either by a single presynaptic input or multiple ones. Postsynaptic Presynaptic 30 0 -55 -70 mV AIS (axon initial segment) No AP Presynaptic Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 7 of 10 Temporal summation of EPSP’s (2) Presynaptic ↓ Postsynaptic Presynaptic 30 0 -55 -70 mV AIS (axon initial segment) AP Presynaptic Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 8 of 10 4  08/07/2019 Neural integration of EPSP’s & IPSP’s - ⑭ EPSP Excitatory postsynaptic potential: Changes that happen in response to positively charged ions (sodium and potassium ions), which moves the membrane potential towards the triggering threshold for an action potential. = F & IPSP Inhibitory postsynaptic potential: Changes that happen in response to negatively charged ions (chloride ions), which moves the resting membrane potential towards a hyperpolarised state and further - away from the triggering threshold. - - *Postsynaptic cell - Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 9 of 10 End of part 2 End of part 2 Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 10 of 10 5  08/07/2019 INSTITUTE OF PSYCHIATRY, PSYCHOLOGY & NEUROSCIENCE Module: Dr Phil Holland Biological Foundations of Mental Health Topic 1: Week 3: Action potentials and Synaptic transmission and neurotransmitter systems Synaptic transmission Part 3 of 5 Part 3 Part 3 Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 2 of 12 1  08/07/2019 Direction of travel from neuron to neuron Presynaptic neuron Axon Triggering of an Dendrites action potential - Cell body Axon initial segment (AIS)O Week 3 Dendrites Cell body Axon initial segment Synaptic transmission and neurotransmitter systems Tera Postsynaptic neuron Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 3 of 12 Voltage gated Na+ channels Na+ sodium K+ Extracellular space Cl- Na+ Na+ Na+ - K potassium + K+ K+ Na+ Na+ Cl- Cl- Cl- chloride Na+ Na+ Na+ - * Voltage-gated * Voltage-gated Na+ channels K+ channels K+ Na+ K+ K+ Na+ K+ Na+ Cl- K+ K+ K+ Intracellular space K+ Cl- Na+ Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 4 of 12 2  08/07/2019 Voltage gated K+ channel & Na+ Na+ sodium K+ Extracellular space Na+ Cl- Na+ K+ potassium Cl- Na+ K+ Na+ Cl- chloride Na+ Cl- Na+ Na+ Na+ Voltage-gated K+ Voltage-gated Na+ channels K+ channels K+ ↑ Electrostatic force K+ Na+ Force of diffusion K+ # Hyperpolarisation: The inside of the cell becomes more negative. K+ K+ Cl- Na+ - Intracellular space K+ - Na+ Depolarisation: The inside of the F cell becomes more positive. K+ Cl- Na+ K+ K+ - Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 5 of 12 * Triggering an action potential 30 Presynaptic 0 Postsynaptic -55 -70 AIS (axon initial segment) mV No AP 30 The AIS is designed to trigger action potentials. It has high concentrations 0 of various types of channels making it uniquely responsive to change and -55 uniquely excitable. -70 mV AP Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 6 of 12 3  08/07/2019 The action potential (1) 1 Resting membrane potential -dete gude 2 Depolarising stimuli 5 Depolarisation reaches - Watche 3 threshold: v-gated Na channels open and Na+ enters neuron 4 Rapid Na+ entry depolarises 4 neuron further 3 1 Na channels inactivate 2 5 (0.5 ms after open) - Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 7 of 12 The action potential (2) Slower responding K+ channels 6 open and K+ moves out of the neuron K channels remain open and 7 more K+ leaves the neuron, hyperpolarising it Voltage-gated K channels close, 6 8 some K+ enters cell through leak channels 9 Normal membrane potential 7 9 8 Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 8 of 12 4  08/07/2019 * Refractory periods Absolute refractory period: Absolute cannot trigger an action potential Results from the inactivation of Na+ channels, and lasts until the resting Relative can trigger an action membrane potential is restored. potential but a greater stimulus is needed to Effects: reach threshold allows the neuron to control its excitability prevents back propagation - Relative refractory period: Results from the hyperpolarisation phase. * Refractory period Lasts until the resting membrane - potential has been restored Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 9 of 12 ~ Phamer Functional states Na+ sodium Na+ Na+ Na+ Closed (resting) Open (active) Inactive (refractory) charge dependant mechanism - blocks the pore Not all channels have all 3 states: voltage-gated Na channels have all 3 & voltage-gated K channels have no inactivation state - Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 10 of 12 5  08/07/2019 - Na channel changes during action potential 1 30 2 30 3 30 0 0 0 mV mV mV -55 -55 -55 -70 -70 -70 Na+ Na+ Na+ * Resting condition Voltage-dependent activation of the gate Depolarisation phase - - - 4 30 5 30 0 0 mV mV -55 -55 -70 -70 Na+ Na+ * Bea Ion channel is blocked, preventing further depolarisation hyperpolarisation phase Na+ sodium Week 3 Synaptic transmission and neurotransmitter systems - Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 11 of 12 End of part 3 End of part 3 Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 12 of 12 6  08/07/2019 INSTITUTE OF PSYCHIATRY, PSYCHOLOGY & NEUROSCIENCE Module: Dr Phil Holland Biological Foundations of Mental Health Topic 1: Week 3: Action potentials and Synaptic transmission and neurotransmitter systems Synaptic transmission - - Part 4 of 5 Part 4 - Part 4 Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 2 of 10 1  08/07/2019 Axonal conductance Unmyelinated fibres Presynaptic neuron Myelinated fibres Axon Dendrites Cell body & Axon initial segment (AIS) Dendrites Cell body Axon initial Axon segment Postsynaptic neuron Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 3 of 10 Action potential conduction (1) normal distribution Graded potential above threshold -55 millivolts = reaches the AIS Axon initial segment (AIS) Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 4 of 10 2  08/07/2019 Action potential conduction (2) Axon initial segment 2 has a very high concentration of voltage-gated sodium channels and voltage- gated potassium channels. Na+ Voltage gated Na+ channels open 2 and Na+ enters the neuron - Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 5 of 10 Action potential conduction (3) 3 Na+ depolarises membrane further 3 opening more Na+ channels Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 6 of 10 3  08/07/2019 Action potential conduction (4) 5 6 Slower voltage-gated potassium channels will now begin to open K+ - 4 - Na+ channel inactivated 4 Depolarisation spreads along the axon 5 K+ channels open, repolarising the membrane 6 (prevents back travel) -- Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 7 of 10 Action potential conduction: Non-myelinated Na+ Cell body Axon Unmyelinated fibres Na+ AIS (axon initial segment) *This is a relatively slow process. K+ Na+ K+ Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 8 of 10 W 4  08/07/2019 Action potential conduction: Myelinated axons - Na+ Fee Saltatory conduction Cell body Axon Na+ Myelin sheath Nodes of Ranvier AIS (axon initial Myelinated segment) fibres Peripheral nervous system: Loss of the Schwann cells action potential Central nervous system: Oligodendrocytes Lif myim disupted Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 9 of 10 End of part 4 End of part 4 Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 10 of 10 5  08/07/2019 INSTITUTE OF PSYCHIATRY, PSYCHOLOGY & NEUROSCIENCE Module: Dr Phil Holland Biological Foundations of Mental Health Topic 1: Week 3: Action potentials and Synaptic transmission and neurotransmitter systems Synaptic transmission Part 5 of 5 Part 5 Part 5 Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 2 of 8 1  08/07/2019 Synaptic transmission in chemical synapses (1) upsi Sun cnicer --electrical Presynaptic neuron Neurotransmitter release Axon Dendrites Cell body Axon initial segment (AIS) Dendrites Cell body Axon initial Axon --- segment Postsynaptic neuron ↑ Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 3 of 8 Synaptic transmission in chemical synapses (2) Calcium has a much higher Presynaptic neuron concentration in the extracellular Action 1 Resting synapse space than the intracellular space. 2 potential Action potential arrives, 2 voltage-gated Ca2+ channels open 1 Ca2+ entry triggers exocytosis of Ca2+ 3 synaptic vesicle content Neurotransmitter diffuses across 4 the synaptic cleft and activates ligand gated ion channels in the Voltage-gated calcium channels Synaptic cleft 3 postsynaptic cell membrane - - Mitochondria 4 aufs s Light - Ca2+ rispers Eigent Vesicles (circle) and neurotransmitters (small dots) Ca2+ sate Ca2+ Calcium Exocytosis: Ca2+ entry triggers exocytosis of Ligand-gated ion channel Postsynaptic neuron synaptic vesicle content Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 4 of 8 2  08/07/2019 Stimulus dependent neurotransmitter release Action Graded Potential Potential Recording electrodes: We’re recording the graded potential that's coming into the cell body, what’s happening at the axon initial segment triggering zone, and the action potentials from the axon. Trigger Zone 0 millivolts The firing mechanism between the presynaptic -40 j ↑ and postsynaptic cell is stimulus-dependent. -80 => 0 millivolts -40 C -80 Higher thushed will crate rae action Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 5 of 8 Neurotransmitter removal Presynaptic neuron primer -un etivemetism a versimp-target & der There are several mechanisms that deal with the Diffusion removal of neurotransmitters: 2 Reuptake of the neurotransmitters into the 1 4 1 presynaptic cell astrocyte Reuptake of the neurotransmitters by the 2 supporting glial cells (e.g. astrocytes) 3 Degrading of neurotransmitters on the 3 postsynaptic membrane Degradation Diffusion of neurotransmitters away from the 4 synaptic cleft and taken up into the bloodstream Postsynaptic neuron Antidepressant that act as serotonin reuptake Voltage-gated calcium channels Ca2+ Calcium inhibitors prevent the reuptake of serotonin, Vesicles (circle) and Ligand-gated ion channel potentiating the effect of its normal release neurotransmitters (small dots) Week 3 Synaptic transmission and neurotransmitter systems Week Topic 1: Action potentials and synaptic 2 – Lorem ipsum transmission 6 of 8 3  08/07/2019 The synaptic transmission: Graded potentials Presynaptic axon 1 Incoming action potential Action potential 1 Action potential triggers a voltage 2 change at the presynaptic terminal 2 Voltage-gated calcium channels Ca2+