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Neurotransmitter Function

Neurotransmitter Function. Outline. A few definitions Neuronal structure Communication within a neuron: The Action Potential Communication between neurons: Neurotransmission Types of Neurotransmitters, Agonists and Antagonists Types of Receptors. A few definitions.

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Neurotransmitter Function

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  1. Neurotransmitter Function Neurotransmitter Function

  2. Outline • A few definitions • Neuronal structure • Communication within a neuron: The Action Potential • Communication between neurons: Neurotransmission • Types of Neurotransmitters, Agonists and Antagonists • Types of Receptors Neurotransmitter Function

  3. A few definitions • Amino acid = A class of organic molecules containing an amino group (-NH2). • Peptide = A chain of two or more amino acids, smaller than proteins. • Protein = A long chain of amino acids which contain carbon, hydrogen, oxygen, nitrogen and usually sulphur. Neurotransmitter Function

  4. A few definitions • Neurotransmitter = A substances released from the axon terminal of a neuron and binds to the receptor. • Enzyme = Protein that controls a chemical reaction, combining or dividing a substance • Ions = An electrically charged particle • positive or negative Neurotransmitter Function

  5. Neuronal Structure • Dendrites receive incoming information from other neurons • Makes up most of the surface area of the neuron • Dendritic spines can number in the thousands Neurotransmitter Function

  6. Neuronal Structure The soma: • processes this information, • maintains integrity of neuronal processes • allows for transmission of neuronal information (action potential) Neurotransmitter Function

  7. Neuronal Structure • The axon transmits information to other neurons • A single axon with branching “collaterals”, but is always a single channel/message. • Teledendria: end branches of axon Neurotransmitter Function

  8. Soma Axon Dendrites Neuronal Structure Neurotransmitter Function

  9. Neuronal Structure • Terminal button or bouton usually near dendritic spine of another neuron (but no touching!) • The terminal button converts action potentials into the release of neurotransmitter. Neurotransmitter Function

  10. At the terminal button • Information is carried by a chemical-electrical process • Whether there is a release of transmitter is dependent on information from efferent neurons • If transmitter is released into synaptic cleft, it will bind to the appropriate receptors located on the dendritic spines Neurotransmitter Function

  11. Communication Within Neurons • A single action potential is usually not enough to release transmitter • There has to be repeated presentation of action potentials for neuronal conduction to occur Neurotransmitter Function

  12. Neurotransmitter Function

  13. Communication Within Neurons • A membrane of a neuron that is inactive is electrically charged--a resting potential. • This potential is about -70mV. • The potential fluctuates depending on the flow and concentration of ions inside and outside the cell. • depolarized or hyperpolarized • Gated channels regulated by receptors control the flow of ions. • Once the potential depolarizes to a particular level, an action potential occurs. Neurotransmitter Function

  14. Communication Within Neurons Why is there a resting potential at all? 1. The flow of ions is mediated by the structure of the cell membrane • Some ions are free to pass though the membrane at any time, others (Na+) are not. • Concentration gradient (Diffusion): Ions will travel (if they can) from an area of high concentration to one of low concentration. Neurotransmitter Function

  15. Communication Within Neurons Why is there a resting potential at all? 2. The flow of ions is also dependent on the relative potentials inside and outside the cell. • Electrostatic pressure (voltage gradient): Positively charged ions attracted to a negative charge, and vice versa. Neurotransmitter Function

  16. Communication Within Neurons • Because the membrane is selectively permeable, the concentration and voltage gradients interact to produce a negative resting potential inside the cell. • The resting potential is also maintained by the sodium-potassium pump. • Pumps Na+ out and K+ in. • Ions remain close to the cell membrane and influence the membrane potential. Neurotransmitter Function

  17. Communication Within Neurons Extra-cellular space: Sodium (Na+) Cloride (Cl-) Calcium (Ca++) Intra-cellular space: Potassium (K+) Anions (A-) Neurotransmitter Function

  18. Communication Within Neurons • When potential depolarizes to -50mV, voltage gated channels are opened for Na+ and K+ • There is an influx of Na+ and an efflux of K+ • These ions move outside of their area of usual concentration Neurotransmitter Function

  19. Neurotransmitter Function

  20. Communication Within Neurons • The opening of channels brings membrane potential to +30mV. • Once the action potential has reached its peak, gated channels close, and begins its return to a resting state. • Extra K+ ions outside the membrane are responsible for a brief hyperpolarization prior to the resting state. Neurotransmitter Function

  21. Neurotransmitter Function

  22. Communication Within Neurons • The action potential is a local (usually dendritic) event • Potential is propagated across the membrane (120meters/second). • Parts of the axon covered by the myelin sheath cannot produce action potentials. • The potential can jump along the length of the axon by Nodes of Ranvier via passive conduction (cable properties). Neurotransmitter Function

  23. Communication Within Neurons • Once enough action potentials reach the terminal button, transmitter is released. • Ca++ (calcium) channels open in the membrane • Ca++ enters and fuses with the synaptic vesicles that are docked to the membrane • Vesicles then release neurotransmitter into the synaptic cleft • Neurotransmitter crosses the cleft and binds to the receptors of the postsynaptic neuron Neurotransmitter Function

  24. Neurotransmitter Function

  25. Communication Within Neurons Axonal conduction obeys two laws: • All or None Law – once triggered, an action potential is transmitted down to the terminal button. • Rate Law – The number of action potentials produced by a neuron determines how strong activation of other neurons will be. Neurotransmitter Function

  26. Activation of Receptors • A receptor is linked to to the opening or closing of an ion channel. • Receptor is activated once a neurotransmitter binds to it. • The membrane potential changes: • Excitatory – depolarizes the cell • Inhibitory – hyperpolarizes the cell • The change in potential is determined by the receptor, not the neurotransmitter Neurotransmitter Function

  27. Activation of Receptors • Excitatory Postsynaptic Potential (EPSP) – due to opening of Na+ channels • Inhibitory Postsynaptic Potential (IPSP) – due to opening of K+ channels • Postsynaptic potentials are brief due to: • Reuptake • Enzymatic deactivation Neurotransmitter Function

  28. Reuptake • Extremely rapid removal of neurotransmitter from the synaptic cleft by the terminal button • Presynaptic transporter molecules pick up the neurotransmitter • Some neurotransmitters are reabsorbed by support cells (astrocytes) Neurotransmitter Function

  29. Enzymatic Deactivation • Only occurs for acetylcholine (ACh) • An enzyme, acetylcholinesterase, is found in the postsynaptic membrane of neurons in the ACh pathways of the brain • This enzyme breaks ACh into its inactive constituents – acetate and choline Neurotransmitter Function

  30. Summation • EPSPs increase the likelihood that a neuron fires • IPSPs decreases this likelihood • Neural integration: Rate at which an axon fires determined by relative activity of EPSPs and IPSPs • Result is either neural activation or inhibition (not the same as behavioural activation or inhibition) Neurotransmitter Function

  31. Neurotransmitter Function

  32. Neurotransmitter Function

  33. Communication Between Neurons Three types of chemicals: • Neurotransmitters – synthesized within the axon, travel short distances, fast acting • Neuromodulators – synthesized within the soma, travel farther distances (diffusion), slower • Peptides • Neurohormones – synthesized in endocrine glands, also travel far distances • Bind to receptors on the cell or nuclear membrane Neurotransmitter Function

  34. Neurotransmitter Agonists • Neurotransmitter action can be mimicked by drugs that are similar in chemical structure • Agonist binds directly to receptors • Indirectly increase the production of neurotransmitter • Example: L-DOPA – increases concentration of DA in the substantia nigra and alleviates symptoms of Parkinson’s disease Neurotransmitter Function

  35. Neurotransmitter Antagonists • Antagonists oppose or inhibit • It may block binding of the neurotransmitter to its receptor • It may prevent reuptake and recycling • Indirectly decrease production • Example: Clozapine blocks DA receptors – used to treat symptoms of schizophrenia (cortical components) Neurotransmitter Function

  36. Amino Acids • Some amino acids don’t need to be converted to have an action on synapses 1. Glutamate 2. GABA (-amino-butyric acid) 3. Glycine • Most synaptic communication is accomplished by amino acids • Fast acting over short distances Neurotransmitter Function

  37. Glutamate • Main excitatory neurotransmitter of the CNS • Found in all CNS structures • Involved in almost all brain functions Neurotransmitter Function

  38. GABA • Inhibition of neurons • Control effects of over-excitation – which can lead to seizures • Found in all CNS structures • Involved in almost all brain functions Neurotransmitter Function

  39. Glycine • Inhibitory: Seems to be secreted by neurons in the lower brain stem at the same time as GABA • Not sure of differences from GABA • No known agonists Neurotransmitter Function

  40. Monoamines • Catecholamines • Dopamine • Norepinephrine • Epinephrine (sort of) • Serotonin • Cell bodies producing these are found primarily in the brain stem and branch profusely • Widespread areas of effect Neurotransmitter Function

  41. Dopamine • Produces both EPSPs and IPSPs depending on the postsynaptic receptor • Implicated in movement, attention, learning and addiction Neurotransmitter Function

  42. Dopamine Main DA systems: 1. Nigrostriatal (Movement – damage causes Parkinson’s Disease) • Cell bodies located in substantia nigra • Project to caudate nucleus and putamen 2. Mesolimbic (Reward system) • Cell bodies in ventral tegmental area • Project to nucleus accumbens (prefrontal subcortex), amygdala, and hippocampus 3. Mesocortical (STM, planning, strategy preparation) • Cell bodies in ventral tegmental area • Project to prefrontal cortex Neurotransmitter Function

  43. Norepinephrine • Sythesized from DA • Cell bodies of most NE neurons are located in regions of the pons and medulla and the thalamus • NE receptors are excitatory and inhibitory • Locus coeruleus in the pons – activation leads to increased vigilance • Arousal: sexual behaviour and food Neurotransmitter Function

  44. Serotonin • 5-hydroxytryptamine (5-HT) • Cell bodies are found in raphe nucleus, pons, and medulla (part of the reticular formation) • Projections are mainly to the cerebral cortex, the hippocampus, and basal ganglia Neurotransmitter Function

  45. Serotonin • Plays a role in many behaviours: • Regulation of mood • Control of eating, sleep, arousal • Regulation of pain • Involved in higher cognition and emotion Neurotransmitter Function

  46. Acetylcholine • Excitatory • Distribution throughout brain • Three areas of importance: • Dorsolateral pons – involved in REM sleep • Basal forebrain – perceptual learning • Medial septum – modulation of hippocampus and formation of memories Neurotransmitter Function

  47. Neuromodulators: Peptides • Endogenous opioids: analgesic properties • Endorphins, enkephalins, and dynorphins • Regulation of pain for different brain areas • Enhancement of fight or flight response • Linked to memory: hippocampus and amygdala Neurotransmitter Function

  48. Neuromodulators: Lipids and Nucleosides • Lipids: fat-like substance, water insoluable • Cannabis: THC (tetrahydrocannabinol) and anandamide (neuronal equivalent) • Nucleosides: Sugar molecule bound with one of two amino acids (purine or pyrimidine) • Adenosine: dilation of blood vessels, especially during sleep • Caffeine: adenosine antagonist producing headaches, drowsiness, and difficulty concentrating Neurotransmitter Function

  49. Neurohormones • Not produced in the brain • Many work in multiple organ systems • Cholecystokinin, Neuropeptide Y, Substance P, Thyroid hormone releasing hormone (TRH), etc. • Typically used in brain areas that control these organs Neurotransmitter Function

  50. Activation of Receptors • A chemical may bind to more than one type of receptor • Different receptors accomplish different functions Neurotransmitter Function

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