Chapter 4 Neural Conduction and Synaptic Transmission

1. Chapter 4Neural Conduction and Synaptic Transmission How Neurons Send and Receive Signals • This multimedia product and its contents are protected under copyright law. The following are prohibited by law: • any public performance or display, including transmission of any image over a network; • preparation of any derivative work, including the extraction, in whole or in part, of any images; • any rental, lease, or lending of the program. Copyright © 2006 by Allyn and Bacon

2. The Neuron’s Resting Membrane Potential • Inside of the neuron is negative with respect to the outside • Resting membrane potential is about -70mV • Membrane is polarized, it carries a charge • Why? Copyright © 2006 by Allyn and Bacon

3. Ionic Basis of the Resting Potential • Ions, charged particles, are unevenly distributed • Factors influencing ion distribution • Homogenizing • Factors contributing to uneven distribution Copyright © 2006 by Allyn and Bacon

4. Ionic Basis of the Resting Potential • Homogenizing • Random motion – particles tend to move down their concentration gradient • Electrostatic pressure – like repels like, opposites attract • Factors contributing to uneven distribution • Membrane is selectively permeable • Sodium-potassium pumps Copyright © 2006 by Allyn and Bacon

5. Ions Contributing to Resting Potential • Sodium (Na+) • Chloride (Cl-) • Potassium (K+) • Negatively charged proteins (A-) • synthesized within the neuron • found primarily within the neuron Copyright © 2006 by Allyn and Bacon

6. The Neuron at Rest • Ions move in and out through ion-specific channels • K+ and Cl- pass readily • Little movement of Na+ • A- don’t move at all, trapped inside Copyright © 2006 by Allyn and Bacon

7. Equilibrium Potential • The potential at which there is no net movement of an ion – the potential it will move to achieve when allowed to move freely • Na+ = 120mV • K+ = -90mV • Cl- = -70mV (same as resting potential) Copyright © 2006 by Allyn and Bacon

8. The Neuron at Rest • Na+ is driven in by both electrostatic forces and its concentration gradient • K+ is driven in by electrostatic forces and out by its concentration gradient • Cl- is at equilibrium • Sodium-potassium pump – active force that exchanges 3 Na+ inside for 2K+ outside Copyright © 2006 by Allyn and Bacon

9. Something to think about • What would happen if the membrane’s permeability to Na+ were increased? • What would happen if the membrane’s permeability to K+ were increased? Copyright © 2006 by Allyn and Bacon

10. Generation and Conduction of Postsynaptic Potentials (PSPs) • Neurotransmitters bind at postsynaptic receptors • These chemical messengers bind and cause electrical changes • Depolarizations (making the membrane potential less negative) • Hyperpolarizations (making the membrane potential more negative) Copyright © 2006 by Allyn and Bacon

11. Generation and Conduction of Postsynaptic Potentials (PSPs) • Postsynaptic depolarizations = Excitatory PSPs (EPSPs) • Postsynaptic hyperpolarizations = Inhibitory PSPs (IPSPs) • EPSPs make it more likely a neuron will fire, IPSPs make it less likely • PSPs are graded potentials – their size varies Copyright © 2006 by Allyn and Bacon

12. EPSPs and IPSPs • Travel passively from their site of origination • Decremental – they get smaller as they travel • 1 EPSP typically will not suffice to cause a neuron to “fire” and release neurotransmitter – summation is needed Copyright © 2006 by Allyn and Bacon

13. Integration of PSPs and Generation of Action Potentials (APs) • In order to generate an AP (or “fire”), the threshold of activation must be reached at the axon hillock • Integration of IPSPs and EPSPs must result in a potential of about -65mV in order to generate an AP Copyright © 2006 by Allyn and Bacon

14. Integration • Adding or combining a number of individual signals into one overall signal • Temporal summation – integration of events happening at different times • Spatial - integration of events happening at different places Copyright © 2006 by Allyn and Bacon

15. What type of summation occurs when: • One neuron fires rapidly? • Multiple neurons fire at the same time? • Several neurons fire repeatedly? • Both temporal and spatial summation occur simultaneously Copyright © 2006 by Allyn and Bacon

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18. The Action Potential • All-or-none, when threshold is reached the neuron “fires” and the action potential either occurs or it does not. • When threshold is reached, voltage-activated ion channels are opened. Copyright © 2006 by Allyn and Bacon

19. The Ionic Basis of Action Potentials • When summation at the axon hillock results in the threshold of excitation (-65mV) being reached, voltage-activated Na+ channels open and sodium rushes in. • Remember, all forces were acting to move Na+ into the cell. • Membrane potential moves from -70 to +50mV. Copyright © 2006 by Allyn and Bacon

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21. The Ionic Basis of Action Potentials • Rising phase: Na+ moves membrane potential from -70 to +50mV. • End of rising phase: After about 1 millisec, Na+ channels close. • Change in membrane potential opens voltage-activated K+ channels. • Repolarization: Concentration gradient and change in charge leads to efflux of K+. • Hyperpolaization: Channels close slowly - K+ efflux leads to membrane potential <-70mV. Copyright © 2006 by Allyn and Bacon

22. Refractory Periods • Absolute – impossible to initiate another action potential • Relative – harder to initiate another action potential • Prevent the backwards movement of APs and limit the rate of firing Copyright © 2006 by Allyn and Bacon

23. The action potential in action • http://intro.bio.umb.edu/111-112/112s99Lect/neuro_anims/a_p_anim1/WW1.htm • http://bio.winona.msus.edu/berg/ANIMTNS/actpot.htm Copyright © 2006 by Allyn and Bacon

24. EPSPs/IPSPs Decremental Fast Passive (energy is not used) Action Potentials Nondecremental Conducted more slowly than PSPs Passive and active PSPs Vs Action Potentials (APs) Copyright © 2006 by Allyn and Bacon

25. Conduction in Myelinated Axons • Passive movement of AP within myelinated portions occurs instantly • Nodes of Ranvier (unmyelinated) • Where ion channels are found • Where full AP is seen • AP appears to jump from node to node • Saltatory conduction • http://www.brainviews.com/abFiles/AniSalt.htm Copyright © 2006 by Allyn and Bacon

26. Structure of Synapses • Most common • Axodendritic – axons on dendrites • Axosomatic – axons on cell bodies • Dendrodendritic – capable of transmission in either direction • Axoaxonal – may be involved in presynaptic inhibition Copyright © 2006 by Allyn and Bacon

27. Synthesis, Packaging, and Transport of Neurotransmitter (NT) • NT molecules • Small • Synthesized in the terminal button and packaged in synaptic vesicles • Large • Assembled in the cell body, packaged in vesicles, and then transported to the axon terminal Copyright © 2006 by Allyn and Bacon

28. Release of NT Molecules • Exocytosis – the process of NT release • The arrival of an AP at the terminal opens voltage-activated Ca++ channels. • The entry of Ca++ causes vesicles to fuse with the terminal membrane and release their contents • http://www.tvdsb.on.ca/westmin/science/sbioac/homeo/synapse.htm Copyright © 2006 by Allyn and Bacon

29. Activation of Receptors by NT • Released NT produces signals in postsynaptic neurons by binding to receptors. • Receptors are specific for a given NT. • Ligand – a molecule that binds to another. • A NT is a ligand of its receptor. Copyright © 2006 by Allyn and Bacon

30. Receptors • There are multiple receptor types for a given NT. • Ionotropic receptors – associated with ligand-activated ion channels. • Metabotropic receptors – associated with signal proteins and G proteins. Copyright © 2006 by Allyn and Bacon

31. Ionotropic Receptors • NT binds and an associated ion channel opens or closes, causing a PSP. • If Na+ channels are opened, for example, an EPSP occurs. • If K+ channels are opened, for example, an IPSP occurs. Copyright © 2006 by Allyn and Bacon

32. Metabotropic Receptors • Effects are slower, longer-lasting, more diffuse, and more varied. • NT (1st messenger) binds > G protein subunit breaks away > ion channel opened/closed OR a 2nd messenger is synthesized > 2nd messengers may have a wide variety of effects Copyright © 2006 by Allyn and Bacon

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34. Reuptake, Enzymatic Degradation, and Recycling • As long as NT is in the synapse, it is active – activity must somehow be turned off. • Reuptake – scoop up and recycle NT. • Enzymatic degradation – a NT is broken down by enzymes. Copyright © 2006 by Allyn and Bacon

35. Small-molecule Neurotransmitters • Amino acids – the building blocks of proteins • Monoamines – all synthesized from a single amino acid • Soluble gases • Acetylcholine (ACh) – activity terminated by enzymatic degradation Copyright © 2006 by Allyn and Bacon

36. Amino Acid Neurotransmitters • Usually found at fast-acting directed synapses in the CNS • Glutamate – Most prevalent excitatory neurotransmitter in the CNS • GABA – • synthesized from glutamate • Most prevalent inhibitory NT in the CNS • Aspartate and glycine Copyright © 2006 by Allyn and Bacon

37. Monoamines • Effects tend to be diffuse • Catecholamines – synthesized from tyrosine • Dopamine • Norepinephrine • Epinephrine • Indolamines – synthesized from tryptophan • Serotonin Copyright © 2006 by Allyn and Bacon

38. Soluble-Gases and ACh • Soluble gases – exist only briefly • Nitric oxide and carbon monoxide • Retrograde transmission – backwards communication • Acetylcholine (Ach) • Acetyl group + choline • Neuromuscular junction Copyright © 2006 by Allyn and Bacon

39. Neuropeptides • Large molecules • Example – endorphins • “Endogenous opiates” • Produce analgesia (pain suppression) • Receptors were identified before the natural ligand was Copyright © 2006 by Allyn and Bacon

40. Pharmacology of Synaptic Transmission • Many drugs act to alter neurotransmitter activity • Agonists – increase or facilitate activity • Antagonists – decrease or inhibit activity • A drug may act to alter neurotransmitter activity at any point in its “life cycle” Copyright © 2006 by Allyn and Bacon

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42. Agonists – 2 examples • Cocaine - catecholamine agonist • Blocks reuptake – preventing the activity of the neurotransmitter from being “turned off” • Benzodiazepines - GABA agonists • Binds to the GABA molecule and increases the binding of GABA Copyright © 2006 by Allyn and Bacon

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44. Antagonists – 2 examples • Atropine – ACh antagonist • Binds and blocks muscarinic receptors • Many of these metabotropic receptors are in the brain • High doses disrupt memory • Curare - ACh antagonist • Bind and blocks nicotinic receptors, the ionotropic receptors at the neuromuscular junction • Causes paralysis Copyright © 2006 by Allyn and Bacon

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