Chapter 48

1. Chapter 48 Neurons, Synapses, and Signaling

2. Overview: Lines of Communication • Cone snail kills prey with venom that disables neurons • Neurons are nerve cells that transfer information within the body • Two types of signals to communicate: electrical (long-distance) chemical (short-distance)

3. The transmission of information depends on the path of neurons along which a signal travels • Processing of information • simple clusters of neurons called ganglia • more complex organization of neurons called a brain

4. Concept 48.1: Neuron organization and structure reflect function in information transfer • The squid possesses extremely large nerve cells and is a good model for studying neuron function

5. Introduction to Information Processing Nervous systems process three stages: sensory input, integration, and motor output 1) Sensors detect external stimuli and internal conditions and transmit information along sensory neurons 2) Sensory information is sent to the brain/ganglia, where interneurons integrate the information 3) Motor output leaves the brain or ganglia via motor neurons, which trigger muscle or gland activity

6. Many animals have a complex nervous system which consists of: • A central nervous system (CNS) where integration takes place; this includes the brain and a nerve cord • A peripheral nervous system (PNS), which brings information into and out of the CNS

7. Fig. 48-3 Sensory input Integration Sensor Motor output Central nervous system (CNS) Effector Peripheral nervous system (PNS)

8. Neuron Structure and Function • Most of a neuron’s organelles are in the cell body • Dendrites - highly branched extensions that receive signals from other neurons • Axon - a much longer extension that transmits signals to other cells at synapses (connection point between cells where information is passed in the form of chemical messengers called neurotransmitters) • An axon joins the cell body at the axon hillock

9. Information is transmitted from a presynaptic cell (a neuron) to a postsynaptic cell (a neuron, muscle, or gland cell) • Most neurons are nourished or insulated by cells called glia

10. Fig. 48-4 Dendrites Stimulus Presynaptic cell Nucleus Axon hillock Cell body Axon Synapse Synaptic terminals Postsynaptic cell Neurotransmitter

11. Fig. 48-5 Form Fits Function - Variation Dendrites Axon Cell body Portion of axon 80 µm Cell bodies of overlapping neurons Sensory neuron Interneurons Motor neuron

12. Ion pumps and ion channels maintain the resting potential of a neuron • Every cell has a voltage (difference in electrical charge) across its plasma membrane called a membrane potential • Messages are transmitted as changes in membrane potential • The resting potential is the membrane potential of a neuron not sending signals

13. Formation of the Resting Potential • In a mammalian neuron at resting potential, the concentration of K+ is greater inside the cell, while the concentration of Na+ is greater outside the cell (Overall Negative Internally) • Sodium-potassium pumps use the energy of ATP to maintain these K+ and Na+ gradients across the plasma membrane • These concentration gradients represent chemical potential energy

14. The opening of ion channels in the plasma membrane converts chemical potential to electrical potential • A neuron at resting potential contains many open K+ channels and fewer open Na+ channels; K+ diffuses out of the cell • Anions trapped inside the cell contribute to the negative charge within the neuron Animation: Resting Potential

15. Fig. 48-6 Key Sodium- potassium pump Na+ Potassium channel Sodium channel K+ OUTSIDE CELL [Na+] 150 mM [Cl–] 120 mM OUTSIDE CELL [K+] 5 mM [A–] 100 mM [K+] 140 mM INSIDE CELL [Na+] 15 mM [Cl–] 10 mM INSIDE CELL (a) (b)

16. Modeling of the Resting Potential • Resting potential can be modeled by an artificial membrane that separates two chambers • The concentration of KCl is higher in the inner chamber and lower in the outer chamber • K+ diffuses down its gradient to the outer chamber • Negative charge builds up in the inner chamber • At equilibrium, both the electrical and chemical gradients are balanced

17. Fig. 48-7 –90 mV +62 mV Inner chamber Outer chamber 150 mM 140 mM 15 mM 5 mM KCI NaCI KCI NaCI Cl– K+ Na+ Cl– Sodium channel Potassium channel (b) Membrane selectively permeable to Na+ (a) Membrane selectively permeable to K+ ( ( ) ) 5 mM 150 mM ENa = 62 mV log log = –90 mV = +62 mV EK = 62 mV 140 mM 15 mM

18. The equilibrium potential (Eion) is the membrane voltage for a particular ion at equilibrium and can be calculated using the Nernst equation: Eion = 62 mV (log[ion]outside/[ion]inside) • The equilibrium potential of K+ (EK) is negative, while the equilibrium potential of Na+ (ENa) is positive

19. In a resting neuron, the currents of K+ and Na+ are equal and opposite, and the resting potential across the membrane remains steady

20. Action potentials are the signals conducted by axons • Neurons contain gated ion channels that open or close in response to stimuli = membrane potential changes. • When gated K+ channels open, K+ diffuses out, making the inside of the cell more negative • Hyperpolarization, an increase in magnitude of the membrane potential

21. Other stimuli trigger a depolarization, a reduction in the magnitude of the membrane potential • For example, depolarization occurs if gated Na+ channels open and Na+ diffuses into the cell • Graded potentials are changes in polarization where the magnitude of the change varies with the strength of the stimulus

22. Fig. 48-9 Stimuli Stimuli Strong depolarizing stimulus +50 +50 +50 Action potential 0 0 0 Membrane potential (mV) Membrane potential (mV) Membrane potential (mV) Threshold Threshold –50 –50 Threshold –50 Resting potential Resting potential Resting potential Depolarizations Hyperpolarizations –100 –100 –100 1 2 3 5 4 0 2 3 4 0 1 5 0 1 3 5 6 2 4 Time (msec) Time (msec) Time (msec) (b) Graded depolarizations (c) Action potential (a) Graded hyperpolarizations

23. Production of Action Potentials • Voltage-gated Na+ and K+ channels respond to a change in membrane potential • When a stimulus depolarizes the membrane, Na+ channels open, allowing Na+ to diffuse into the cell • The movement of Na+ into the cell increases the depolarization and causes even more Na+ channels to open • A strong stimulus results in a massive change in membrane voltage called an action potential

24. Fig. 48-9c Strong depolarizing stimulus +50 Action potential Action Potential Occurs if a stimulus causes the membrane voltage to cross a particular threshold 0 Membrane potential (mV) –50 Threshold Resting potential –100 0 2 4 5 6 1 3 Time (msec) (c) Action potential

25. Action Potential • Brief all-or-none depolarization of a neuron’s plasma membrane • Action potentials are signals that carry information along axons (Not to other cells) • Hundreds of action potentials per second • Frequency of action potentials = strength of a stimulus • An action potential can be broken down into a series of stages

26. Fig. 48-10-5 Key Na+ K+ Falling phase of the action potential 4 Rising phase of the action potential 3 +50 Action potential 3 0 Membrane potential (mV) 2 4 Threshold –50 1 1 5 Resting potential Depolarization 2 –100 Time Extracellular fluid Sodium channel Potassium channel Plasma membrane Cytosol Inactivation loop Undershoot 5 Resting state 1

27. At resting potential • Most voltage-gated Na+ and K+ channels are closed, but some K+ channels (not voltage-gated) are open

28. When an action potential is generated • Voltage-gated Na+ channels open first and Na+ flows into the cell • During the rising phase, the threshold is crossed, and the membrane potential increases • During the falling phase, voltage-gated Na+ channels become inactivated; voltage-gated K+ channels open, and K+ flows out of the cell

29. During the undershoot, membrane permeability to K+ is at first higher than at rest, then voltage-gated K+ channels close; resting potential is restored Refractory period after an action potential, a second action potential cannot be initiated Result of a temporary inactivation of the Na+ channels

30. Useful Simulations BioFlix: How Neurons Work Animation: Action Potential

31. Conduction of Action Potentials • Travels long distances by regenerating itself • At the site where the action potential is generated, usually the axon hillock, an electrical current depolarizes the neighboring region of the axon membrane • Inactivated Na+ channels behind the zone of depolarization prevent the action potential from traveling backwards • Only travels toward the synaptic terminals

32. Fig. 48-11-3 Axon Plasma membrane Action potential Cytosol Na+ Action potential K+ Na+ K+ Action potential K+ Na+ K+

33. Conduction Speed • The speed of an action potential increases with the axon’s diameter • In vertebrates, axons are insulated by a myelin sheath, which causes an action potential’s speed to increase • Myelin sheaths are made by glia— oligodendrocytes in the CNS and Schwann cells in the PNS

34. Fig. 48-12a Node of Ranvier Layers of myelin Axon Schwann cell Schwann cell Nodes of Ranvier Nucleus of Schwann cell Axon Myelin sheath Myelinated axon (cross section)

35. Action potentials are formed only at nodes of Ranvier, gaps in the myelin sheath where voltage-gated Na+ channels are found • Jump between the nodes of Ranvier in a process called saltatory conduction Schwann cell Depolarized region (node of Ranvier) Cell body Myelin sheath Axon

36. Neurons communicate with other cells at synapses • Electrical synapses, the electrical current flows from one neuron to another • Chemical synapses, a chemical neurotransmitter carries information across the gap junction Most synapses are chemical synapses

37. Fig. 48-14 Postsynaptic neuron Synaptic terminals of pre- synaptic neurons 5 µm

38. The presynaptic neuron synthesizes and packages the neurotransmitter in synaptic vesicles located in the synaptic terminal • The action potential causes the release of the neurotransmitter • The neurotransmitter diffuses across the synaptic cleft and is received by the postsynaptic cell Animation: Synapse

39. Fig. 48-15 5 Na+ K+ Synaptic vesicles containing neurotransmitter Presynaptic membrane Voltage-gated Ca2+ channel Postsynaptic membrane Ca2+ 1 4 6 2 3 Synaptic cleft Ligand-gated ion channels

40. Postsynaptic Potential • Binding of neurotransmitters to ligand-gated ion channelsin the postsynaptic cell • Neurotransmitter binding causes ion channels to open, generating a postsynaptic potential • Excitatory postsynaptic potentials (EPSPs) are depolarizations that bring the membrane potential toward threshold • Inhibitory postsynaptic potentials (IPSPs) are hyperpolarizations that move the membrane potential farther from threshold

41. End of a neurotransmitter…or is it? • After release, the neurotransmitter • May diffuse out of the synaptic cleft • May be taken up by surrounding cells • May be degraded by enzymes

42. Summation of Postsynaptic Potentials • Unlike action potentials, postsynaptic potentials are graded and do not regenerate • Most neurons have many synapses on their dendrites and cell body • A single EPSP is usually too small to trigger an action potential in a postsynaptic neuron • If two EPSPs are produced in rapid succession, an effect called temporal summation occurs

43. Fig. 48-16ab Terminal branch of presynaptic neuron E1 E1 E2 E2 Axon hillock Postsynaptic neuron I I 0 Action potential Threshold of axon of postsynaptic neuron Membrane potential (mV) Resting potential –70 E1 E1 E1 E1 (a) Subthreshold, no summation (b) Temporal summation

44. In spatial summation, EPSPs produced nearly simultaneously by different synapses on the same postsynaptic neuron add together • The combination of EPSPs can trigger an action potential • IPSP can counter the effect of an EPSP • May or may not reach threshold and generate an action potential

45. Fig. 48-16cd E1 E1 E2 E2 I I 0 Action potential Membrane potential (mV) –70 E1 E1 + I E1 + E2 I (d) Spatial summation of EPSP and IPSP (c) Spatial summation

46. Modulated Synaptic Transmission Indirect synaptic transmission - A neurotransmitter binds to a receptor that is not part of an ion channel • Second messenger in the postsynaptic cell is activated ex) cAMP • Effects of indirect synaptic transmission have a slower onset but last longer

47. Neurotransmitters • Same neurotransmitter can produce different effects in different types of cells • 5 major classes of neurotransmitters (~100): 1) acetylcholine 2) Biogenic amines 3) Amino acids 4) Neuropeptides 5) Gases

48. Table 48-1

49. Acetylcholine • Acetylcholine is a common neurotransmitter in vertebrates and invertebrates • In vertebrates it is usually an excitatory transmitter. Ex) muscles (except Heart) Bacteria produce toxins that causes botulism Botox

50. Biogenic Amines – Derived from Animo Acids • Include epinephrine, norepinephrine, dopamine, and serotonin • They are active in the CNS and PNS • LSD binds like serotonin to produce hallucinatory effects. • Parkinson’s lack of dopamine • Treat depression with drugs to increase concentration of Bio Amines.