Cellular Communication & Neurotransmission (Biopsychology) PDF

Biopsychology Cellular Communication & Neurotransmission Lecture Overview Ions Neuron Structure Membrane Potential & Resting Potential The Action Potential The Synapse Receptors Neurotransmitters  Ion – a particular (atom) that has an electrical charge (may be...

Biopsychology Cellular Communication & Neurotransmission Lecture Overview Ions Neuron Structure Membrane Potential & Resting Potential The Action Potential The Synapse Receptors Neurotransmitters  Ion – a particular (atom) that has an electrical charge (may be positive or negative) Some Prereq Concepts  https://www.youtube.com/watch? v=6qS83wD29PY Dendrites Myelin Pre- Sheath synaptic Terminals Neuron Nodes of Ranvier (Axon Terminals / Terminal Buttons) Structure Axon Nucleus Axon Hillock Pre-synaptic terminals also referred to as ‘Axon Terminals’ or ‘Terminal Buttons’ Synapses Synapse = junction between neurons where electrochemical signals are exchanged / transmitted  The neuronal membrane is made up of a lipid bilayer (2 layers of lipid molecules) Neurons are surrounded by ‘extracellular fluid’ which contains a higher concentration of ‘cations’ (positively charged) The cytoplasm on the inner side of the membrane Neuronal contains a higher concentration of ‘anions’ (negatively Membrane charged). Structure Lipid Bilaye r https://www.youtube.com/watch? v=tIzF2tWy6KI  Ion channels in the membrane allow for the exchange of specific ions between the intracellular and extracellular space Ion Channels  The typical ‘Resting Potential’ across the neuronal membrane (i.e. difference in electrical charge when the neuron is doing nothing / receiving no input) is -70 millivolts At rest the neuronal membrane is described as ‘polarised’ Resting Membrane Potential Lipid Bilaye r **For a neuron to ‘fire’ the membrane potential needs to reverse along the axon (full polarity reversal from negative to positive)  How is the resting potential maintained? 4 Different types of Ions with different properties 1. Chloride (Cl-) are negatively charged and move freely across the membrane through Cl- channels Resting under the forces of diffusion and electrostatic pressure Membrane 2. Potassium (K+) are positively charged and move Potential freely across the membrane through K+ channels under the forces of diffusion and electrostatic pressure Diffusion and electrostatic pressure together work to ensure that similar ions do not cluster together If it were just these two, the membrane potential would be 0…  Cl- K K Cl- + K + K Cl- + Cl- K Cl- + + K + Resting Membrane Potential A- Cl- K Cl- K + K Cl- + K A- K + Cl- Cl- K + + +  How is the resting potential Maintained? 4 Different types of Ions with different properties 3. Negatively charged Anions (A-) produced within the neuron, have no way of leaving the neuron  very high Resting concentration of negatively charged ions inside Membrane 4. Sodium Ions (NA+) are positively charged do not move that freely. Instead they move via a Sodium- Potential Potassium pump which actively exchanges NA+ and K+ For every 2 K+ brought inside the neuronal membrane, 3 NA+ are pumped out Together these properties ensure a negative resting potential  Higher concentration of positively charged ions NA+ NA+ NA+ NA+ Cl- Cl- NA+K NA+ K NA+ + NA+ K + NA+ K Cl- + Cl- K Cl- + + K + Resting Membrane Potential A- A- A- A- A- A- A- Cl- NA+ K Cl- NA+ K +NA+ K A- Cl- + A- K A- A-+ Cl- K Cl- + + K + Higher concentration of negatively charged ions  Neurons communicate Electrochemical Signals which involves the receipt of chemical messengers via the dendrites followed by an electrical event known as an ‘Action Potential’ that propagates down the axon resulting in the release of chemical messengers by the pre- synaptic terminals Neuronal https://www.youtube.com/watch?v=6qS83wD29PY Communica tion Action potentials are characterised by a series of rapid voltage reversals along the axon due to an exchange of ions across the membrane https://www.youtube.com/watch?  Action Potentials “all or nothing” Can be described as on or off Can be described as 1 or 0 Basis of Computationalism and modern cognitive psychology & neuroscience Neuronal https://www.youtube.com/watch?v=6qS83wD29PY Communica tion Action potentials are characterised by a series of rapid voltage reversals along the axon due to an exchange of ions across the membrane  Difference between an electrical signal along wires and the electrical signal of an action potential along a neuron: Neuronal https://www.youtube.com/watch?v=6qS83wD29PY Communica Electrical wires conduct a flow of electrons we know as electricity or electrical current. Neurons tion conduct impulses that are electrical in nature. A neuron's impulse or signal is called an action potential. This action potential is electric in nature but it involves ion movement and not electron movement  Harvard 13 Minute video describing action potential: https://www.youtube.com/watch? v=oa6rvUJlg7o Neuronal https://www.youtube.com/watch?v=6qS83wD29PY Communica tion Action potentials are characterised by a series of rapid voltage reversals along the axon due to an exchange of ions across the membrane  1. Dendrites contain receptors that respond to naturally occurring chemical messengers called ‘neurotransmitters’ Action Potential 2. Neurotransmitters (or drugs that mimic them) can cause ion channels to open leading to short, localised changes in the membrane potential called Graded Potentials)  Graded Potentials Small, localised changes in membrane potential that don’t trigger a full reversal of membrane potential Excitatory postsynaptic potentials (EPSPs) Action Involved depolarisation of the neuronal membrane EPS Potential (membrane potential becomes more positive)  P IPS P IPS EPS closer to an action IPS Inhibitory potential postsynaptic P P P potentials (IPSPs) EPS IPS P Involved P hyperpolarisation of the EPS neuronal membrane P (membrane potential becomes more negative)  further away from an action  Summation of Graded Potentials EPS Action P Potential EPS 4 P 0 EPS 0 Action P Potential EPS P - 55- 70 Action potential is an all or nothing response! Threshold for all or nothing response = -55mV Axon Hillock has a high concentration of voltage-gated ion channels that open when the membrane potential reaches threshold  1. Resting State: Membrane Potential is -70mV 2 2. Rising Phase Phases of EPSPs arriving at the Action the axon hillock together are 1 summed. Potential If the threshold of - 55mV is reached, then NA+ channels are opened and an action potential is generated in an all During thisfashion. or nothing phase, the neuronal membrane depolarises rapidly reaching a maximum voltage level of approx +40mV  3. Falling Phase: During this phase, sodium channels close and potassium 3 K+ channels open, 2 allowing positive ions to flow out and Phases of the membrane undergoes the Action repolarisation as it returns towards 1 Potential the resting potential 4 (-70mV) 4. Refractory Period: The neuron overshoots the resting potential entering a state of During this phase it is very difficult to generate an action hyperpolarisation potential until the resting potential returns https://www.youtube.com/watch?v=W2hHt_PXe5o  3. Action Potentials are generated at the Axon Hillock when the summation of EPSPs reaches the ‘threshold’. The AP then propagates along the Axon towards the Pre- synaptic Terminals Action Potential  4. The axon is covered by a lipid-rich, insulating sheath of Myelin which serves to speed up the propagation of action potentials Action Potential 5. Due to the insulating myelin sheath, the axon membrane is only exposed at small junctions called ‘Nodes of Ranvier’ (which have a high concentration of ion channels)  6. The action potential occurs at each node and ‘jumps’ along the axon – a process called Saltatory Conduction – until it reaches the pre-synaptic terminal Action Potential https://www.youtube.com/watch?v=iBDXOt_uHTQ  Pre-synaptic Terminal Synaptic Vesicles The Neurotransmitte rs Synapse Overview Pre-synaptic terminal contains structures called synaptic vesicles Synaptic vesicles are filled with chemical messenger  Pre-synaptic Terminal Synaptic Vesicles The Neurotransmitte rs Synapse Synaptic Cleft Overview When the action potential reaches the pre-synaptic terminal, this causes the release of neurotransmitters from the synaptic vesicles into the ‘synaptic cleft’ (space between the presynaptic and post synaptic membrane)  Pre-synaptic Terminal Synaptic Vesicles The Neurotransmitte rs Synapse Receptors Synaptic Cleft Overview Neurotransmitters released into the synaptic cleft act as ‘ligands’ – chemical messengers that bind to receptors on the post-synaptic neuronal membrane and cause changes in the post-synaptic neuron  Types of Synapses  What are Neurotransmitters? What is the life cycle of a neurotransmitter? Stages of Stage 1: Synthesis & Storage Neurotransmissi on Stage 2: Release Stage 3: Activation of Receptors Stage 4: Deactivation of Neurotransmitter  What are Neurotransmitters? Endogenous chemicals used often referred to as ‘chemical messengers’ that bind to ‘receptors’. “a substance that is released by a neuron that affects a specific target in a specific manner. A target can be either What are another neuron or an effector organ, such as muscle or gland” (Kandel, 2021, p. 422) Neurotran The effects of a neurotransmitter on a post-synaptic target s-mitters? can be excitatory or inhibitory Excitatory neurotransmitters depolarize the post synaptic neuron (stimulate it) Inhibitory neurotransmitters hyperpolarise the post- synaptic neuron (inhibit it) Some neurotransmitters can be classified as inhibitory or excitatory, depending on the receptor  Criteria for Classification of Neurotransmitters 1. Synthesised in the pre-synaptic neuron and stored in synaptic vesicles What are 2. When released (via exocytosis) in sufficient concentrations it elicits a response from the Neurotran target neuron or effector (e.g. muscle) s-mitters? 3. When administered experimentally it produces the same effect 4. Mechanisms exist to remove the chemical from the synaptic cleft  Neurotransmitters vs Hormones Both chemical messengers NTs operate in the nervous system, Hormones operate in the blood system (circulatory What are system) Neurotran NTs are released into the synaptic cleft, Hormones are released into the blood stream s-mitters? NTs are produced by neurons, Hormones are produced by endocrine glands NTs travel short distances, Hormones can travel long distances NTs are fast acting but effects are short lived. Hormones are slow acting but effects are longer  1. Small Molecule Neurotransmitters 1.1 Amino Acids: Glutamate (Glu) – Excitatory Gamma-aminobutyric acid (GABA) – Inhibitory Glycine (Gly) – Inhibitory Common 1.2 Amines: (Synthesised from amino acids) Neurotran 1.2.1 Monoamines: Serotonin (5-HT) – Mostly Inhibitory s-mitters Histamine (H) – Excitatory 1.2.2 Catecholamines: Dopamine (DA) – Excitatory and Inhibitory Noradrenaline (NA) / Norepinephrine (NE) – Excitatory and inhibitory Adrenaline / Epinephrine – Excitatory 1.3 Acetylcholine (ACh) – Excitatory & Inhibitory  2. Neuropeptides Larger than small molecule NTs Made up of multiple amino acids Common Opioids - Inhibitory Neurotran ** Lots of hormones are neuropeptides s-mitters 3. Transmitter Gases Carbon Monoxide Nitric Oxide  Where are neurotransmitters made? Neurotransmitters are manufactured within the synaptic vesicles in the Axon Terminals. Stage 1: Enzymes, produced in the cell body and transportedto the axon terminal via structures Synthesis called microtubules, are used to convert NT pre-cursor molecules into NTs & Storage Pre-cursors for Small Molecule NTs are taken into the axon terminals where neuropeptide pre-cursors are made in the cell body alongside the enzymes.  1. Nucleus: Contains DNA Mitochondria which codes for what proteins Produce energy the cell should make. Releases the code via mRNA Stage 1: 2. Rough Endoplasmic Synthesis Reticulum (RER): Receives mRNA and & Storage makes various proteins 3. Golgi Bodies: Stores proteins and The Soma packages them into vesicles 4. Microtubules Transports proteins/vesicles from the soma to the axon terminals  Stage 1: Synthesis & Storage Purves et al. 2001) 1.Nucleus instructs RER to make enzymes (proteins) Small which are then packaged in the golgi apparatus Molecule 2. Enzyme proteins are transported to the axon terminal via the microtubules NTs 3. In the pre-synaptic terminal, enzymes are used to convert pre-cursor molecules into NTs which are then packaged into vesicles. The precursor molecules originate outside the neuron and are taken in via  Stage 1: Synthesis & Storage Purves et al. 2001) 1.Nucleus instructs RER to make neuropeptide pre- Neuropept cursors and enzymes which are then packaged into ide NTs vesicles 2. Vesicles are transported to the axon terminal via microtubules 3. In the pre-synaptic terminal, enzymes trigger a chemical reaction to convert peptide pre-cursors into neuropeptide NTs)  When an action potential reaches the axon terminal, it causes calcium channels to open allowing calcium ions to enter the neuron Incoming calcium ions bind to a pre-existing molecule called ‘calmodulin’ to form the Stage 2: ‘calcium calmodulin complex. Release of The calcium calmodulin NTs complex binds to the synaptic vesicles, bringing them closer to the pre-synaptic membrane NTs are released into the synaptic cleft via a process called exocytosis  Neurotransmitters diffuse across the synaptic cleft and bind to receptors (proteins) embedded in the post synaptic membrane Receptors have binding sites for ligands (chemicals that carry messages and activate receptors) Stage 3: Activation of receptors causes subsequent changes in the post synaptic neuron via effects on ion channels Activation of Effects may be excitatory or Receptors inhibitory  Ionotropic Receptors Also known as ligand gated ion channels Stage 3: Ion channels that have a Activation binding site for ligands Binding of NTs has a direct of impact on the neuron via Receptors opening or closing of the ion channels  Change in the Membrane potential Purves et al. 2001  Metabotropic Receptors Also known as ‘G-Coupled’ Receptors Made of a protein embedded in the membrane attached to an intracellular molecule called a ‘G Protein’ Stage 3: Receptor activation causes the G-protein to Activation detach of G-proteins may interact directly with nearby ion Receptors channels G-proteins may also interact with other proteins to create intracellular messengers that in turn affect ion channels or cell activities Purves et al. 2001  Stage 3: Activation https://www.youtube.com/watch?v=NXOXZ- of kaSVI&t=3s Receptors  Neurotransmitters remain active for a short period of time before becoming deactivated via one of many mechanisms Diffusion: The NT moves away from the synaptic cleft and therefore can no longer act on Stage 4: the receptor Deactivati Degradation: Enzymes break down the NT into on of NTs its component parts Reuptake: The NT is actively taken back up into the pre-synaptic neuron and is recycled / re-used Removal: Neighbouring Glial Cells (support cells) bind to the NT and remove it from the cleft  Acetylcholine Synthesis: Acetylcholine is synthesised in the axon terminal from two components commonly found in food Example: - Acetyl Coenzyme A (Acetate from acidic foods e.g. apples) Acetylcholi - Choline (Fatty products e.g. Fish & Egg Yolk) ne Synthesis involves Acetylcholine the choline acetyl Deactivation: transferase (ChAT) (ACh) Acetylcholine is broken down into acetate and choline in the synaptic cleft by the enzyme acetyl cholinesterase  Products taken back up and reused  Acetylcholine Receptors Nicotinic Receptors These are ionotropic Activation usually results in excitatory post Example: synaptic potentials Named because Nicotine interacts with them. Acetylcholi ne Muscarinic Receptors These are metabotropic (ACh) Many different sub types – some excitatory and some inhibitory Named after Muscarine – a toxin found in some mushrooms that can affect autonomic functioning.  The Neuromuscular Junction Example: Acetylcholi https://www.youtube.com/watch?v=E6SuVmeqs2o ne (ACh) https://www.youtube.com/watch?  Cholinergic Systems Example: Acetylcholi https://www.youtube.com/watch?v=E6SuVmeqs2o ne (ACh) Drugs that inhibit cholinesterase have been developed to treat Alzheimer’s Disease i.e. to prevent the breakdown of acetylcholine https://www.youtube.com/watch?v=6WFhhL- enlQ  Dopamine Synthesis: Dopamine is synthesised in the nerve terminal from a pre-cursor called L-Dopa which in turn is made from Tyrosine (an amino acid found in Example: foods (meats, beans, nuts, cheese) Dopamine Dopamine Deactivation: Dopamine is broken down by three enzymes The product of the breakdown is excretion via urine Some excess dopamine can be taken back up into the pre-synaptic terminal  Dopamine Receptors: Dopamine activity is mediated by g-coupled, metabotropic receptors Example: There are at least 5 subtypes, called D1, D2, D3, D4 Dopamine and D5 receptors Different receptor subtypes are thought to be implicated in different functions and disorders (Mishra et al., 2018) D1 and D5 are excitatory D2, D3 and D4 are inhibitory  Dopaminergic Systems Example: Dopamine https://www.youtube.com/watch?v=E6SuVmeqs2o (DA) L Dopa is a drug used to treat Parkinsons disease – aims to increase production of dopamine https://www.youtube.com/watch?v=Wa8_nLwQIpg  Serotonin Synthesis: Serotonin is synthesised in the nerve terminal from an Amino acid called Triptophan (found in meat, dairy, fruits and seeds) Example: Serotonin Serotonin Deactivation: (5-HT) Serotonin is deactivated via a re-uptake mechanism involving a serotonin transporter pump on the pre-synaptic neuron  Serotonin Receptors Serotonin interacts with a family of at least 7 receptors called 5-HT receptors Example: Most of these are G-Coupled metabotropic Serotonin receptors (5-HT) One is an Ionotropic Receptors Some of the receptors are excitatory, some are inhibitory  Serotonergic Systems Example: Serotonin https://www.youtube.com/watch?v=Xkl_x6wC0Lg (5-HT) https://www.youtube.com/watch?v=Xkl_x6wC0Lg  Noradrenaline Synthesis: Noradrenaline is synthesised from dopamine in the axon terminal Example: Noradrenal Noradrenaline Deactivation: ine Noradrenaline is deactivated via a re-uptake (NA) mechanism involving a noradrenergic transporter  Noradrenaline Receptors Noradrenaline interacts with a family of at least 3 receptors, all of which are G-Coupled metabotropic receptors Example: Noradrenal These are called alpha1, alpha2 and beta receptors ine Each have multiple sub types (NA) Some of the receptors are excitatory, some are inhibitory  Noradrenergic Systems Example: Noradrenal https://www.youtube.com/watch?v=m8kthApqQys ine (NA) https://www.youtube.com/watch?v=m8kthApqQys  What should I know? 1. Label the Neuron, including substructures in the cell body (soma), axon and axon terminals 2. Identify the functions associated with key parts of the neuron in relation to cellular communication and neurotransmission Summing 3. Recognise key terminology relating to cellular communication and associated definitions Up 4. Identify the structure of the neuronal membrane https://www.youtube.com/watch?v=m8kthApqQys 5. Define key properties of the neuron at rest, including the resting potential and relative concentration of positive and negative ions 6. Identify and explain what the term ‘graded potential’ means and how a graded potential is generated 7. Identify and outline the events that lead to the generation of an action potential, including the phases of the action potential 8. Define and outline the process of saltatory conduction 9. Identify and label components of the synapse 10.Define what a neurotransmitter is and how it differs from a hormone.  What should I know? 11.Identify the effects that neurotransmitters can have on the post synaptic neuronal membrane. 12.Identify where and how neurotransmitters are synthesised and stored prior to release (key structures and the role of each) Summing 13.Identify the role of the action potential in releasing neurotransmitters Up 14.Identify the two classes of ‘receptors’ and the key https://www.youtube.com/watch?v=m8kthApqQys differences between them 15.Identify the main mechanisms for deactivating neurotransmitters 16.Identify the origin structures in the brain for key neurotransmitters (Acetylcholine, Dopamine, Serotonin and Noradrenaline)  Kolb and Wishaw (2021) Fundamentals of Neuropsychology Chapter 4 & 5 OR Reading Kolb et al. (2022) Introduction to the Brain & Behaviour Chapter 3,4,& 5 https://www.youtube.com/watch?v=m8kthApqQys Supplementary / E-Books Carlson & Birkett (2017) Physiology of Behaviour Chapter 2 Pinel & Barnes (2021) Biopsychology Chapter 4 For the ambitious!! Bear et al. (2020) Neuroscience: Exploring the Brain