1. PowerPoint ® Lecture Slides prepared by Janice Meeking, Mount Royal College C H A P T E R Copyright © 2010 Pearson Education, Inc. 11 Fundamentals of the Nervous System and Nervous Tissue: Part A

2. Copyright © 2010 Pearson Education, Inc. Neurophysiology Neurons are highly irritable (responsive to stimuli) Action potentials, or nerve impulses, are: Electrical impulses carried along the length of axons Always the same regardless the source or type of stimulus

3. Copyright © 2010 Pearson Education, Inc. Basic principals of electricity The human body is electrically neutral (same number of positive and negative charges) There are areas that are either negatively or positively charged. Opposite charges attract each other Energy is required to separate opposite charges across a membrane

4. Copyright © 2010 Pearson Education, Inc. Electricity Definitions Voltage (V) – measure of potential energy generated by separated charge Voltage is always measured between 2 points and it is called – potential difference or potential The greater the difference between the 2 points the higher the voltage Current (I) – the flow of electrical charge between two points This flow of electrical charges can be used to perform work (ex. light) Resistance (R) – a material's opposition to the flow of electric current Insulator – substance with high electrical resistance Conductor – substance with low electrical resistance

5. Copyright © 2010 Pearson Education, Inc. Electrical Current and the Body Reflects the flow of ions rather than electrons There is a potential on either side of membranes when: The number of ions is different across the membrane The membrane provides a resistance to ion flow

6. Copyright © 2010 Pearson Education, Inc. Membrane ion channels Ion channels – membrane proteins Large with several sub-units Sometimes part of the molecule forms a “gate” that changes the shape to open and close the channel http://hebb.mit.edu/courses/8.515/lecture1/img013.jpg

7. Copyright © 2010 Pearson Education, Inc. Types of plasma membrane ion channels Passive, or leakage, non gated channels – always open Gated channels Chemically gated / ligand gated channels – open with binding of a specific chemical (neurotransmitter in case of the nervous tissue) Voltage-gated channels – open and close in response to membrane potential Mechanically gated channels – open and close in response to physical deformation of receptors Each type of channel is selective – only a certain ion/ions are allowed to pass

8. Copyright © 2010 Pearson Education, Inc. Gated Channels When gated channels are open: Ions move quickly across the membrane Movement is follows their electrochemical gradients Ions move along chemical concentration gradient – from high concentration to a low one Ions move along electrical gradient – towards an area of opposite electrical charge An electrical current is created Voltage changes across the membrane

9. Copyright © 2010 Pearson Education, Inc. Resting Membrane Potential (V r ) The potential difference (–70 mV) across the membrane of a resting neuron – membrane is polarized Minus sign indicates that the inside of the membrane is negatively charged compared to the outside The value can be different in different cells (-40 - -90mv) It is generated by different concentrations of Na +, K +, Cl , and protein anions (A  ) RMP exists only across the membrane – the bulk solutions in the cell are neutral

10. Copyright © 2010 Pearson Education, Inc. Resting Membrane Potential Differential permeability of membrane Impermeable to A – Slightly permeable to Na + (through leakage channels) 75 times more permeable to K + (more leakage channels) Freely permeable to Cl – The reason there is no equilibrium in the ion concentration is because of ATP-driven Na + - K + pump that ejects 3 Na + out of the cell and 2 K + into the cell

11. Copyright © 2010 Pearson Education, Inc. Resting Membrane Potential (V r ) Figure 11.8

12. Copyright © 2010 Pearson Education, Inc. Changes in Membrane Potential Changes are caused by three events – all relative to RMP Depolarization – the inside of the membrane becomes less negative Repolarization – the membrane returns to its resting membrane potential Hyperpolarization – the inside of the membrane becomes more negative than the resting potential

13. Copyright © 2010 Pearson Education, Inc. Membrane Potentials: Signals Used to integrate, send, and receive information Membrane potential changes are produced by: Changes in membrane permeability to ions Alterations of ion concentrations across the membrane Types of signals graded potentials – incoming signals over short distance action potentials – long-distance signals

14. Copyright © 2010 Pearson Education, Inc. Graded Potentials Short-lived, local changes in membrane potential Decrease in intensity with distance Magnitude varies directly with the strength of the stimulus the stronger the stimulus, the more voltage changes and farther the current flows Sufficiently strong graded potentials can initiate action potentials

15. Copyright © 2010 Pearson Education, Inc. Graded Potentials A small area of the neuron membrane has been depolarized by a stimulus (can be electrical, chemical, mechanical etc.) Current will flow on both sides of the membrane – positive ions will move toward negative ones and vice versa. Most of the charge is lost through leakage channels That makes the current decremental – dies out with increasing distance Only travel over short distances

16. Copyright © 2010 Pearson Education, Inc. Action Potentials (APs) When a neuron is adequately stimulated, its membrane permeability changes by opening voltage-gated channels. There is a transition from graded potential (incoming message) to action potential This transition usually occurs in the axon hillock

17. Copyright © 2010 Pearson Education, Inc. Action Potentials (APs) The way to send signals over a long distance Action potentials are only generated by muscle cells and neurons (have excitable membrane) The AP is a brief reversal of membrane potential with a total amplitude of 100 mV (from -70- mv to +30) They do not decrease in strength over distance An action potential in the axon of a neuron is a nerve impulse Very short event – few milliseconds

18. Copyright © 2010 Pearson Education, Inc. Action Potential: Resting State Na + and K + voltage-gated channels are closed Open leakage channels (passive) accounts for small movements of Na + and K + Each Na + channel has two voltage-regulated gates (See figure 11.11 p 400-401 in book) Activation gates (fast) closed in the resting state Respond to depolarization by opening Inactivation gates (slow) open in the resting state Blocks the channel while it is open Depolarization opens and than deactivates sodium channel

19. Copyright © 2010 Pearson Education, Inc. Action Potential: Depolarization Phase Axon membrane is depolarized by local current which results in the opening of sodium channels At this point - Na + gates are opened; K + gates are closed Na + enters the cell (influx) The influx changes the charge inside causing more Na + channels to open The interior of the membrane becomes less negative until it reaches the threshold Threshold – a critical level of depolarization (-55 to -50 mV)

20. Copyright © 2010 Pearson Education, Inc. Threshold Subthreshold stimulus —weak local depolarization that does not reach threshold Threshold stimulus —strong enough to push the membrane potential toward and beyond threshold AP is an all-or-none phenomenon —action potentials either happen completely, or not at all

21. Copyright © 2010 Pearson Education, Inc. Action Potential: Depolarization Phase At threshold, depolarization becomes self-generating After being initiated by the stimulus, depolarization is driven by the Na + influx: More Na + enters more channels are open until all are Na + permeability at this point is 1000 higher than in resting That result in changing the negative internal environment to a positive one of +30mv Sharp action potential

22. Copyright © 2010 Pearson Education, Inc. Action Potential: Repolarization Phase The rising phase of AP persist for about 1ms. Than, the slow sodium inactivation gates close Membrane permeability to Na + declines to resting levels Net influx of sodium stops completely AP spike stop rising As sodium gates become inactive, slow voltage-sensitive K + gates open K + exits the cell and internal negativity of the resting neuron is restored

23. Copyright © 2010 Pearson Education, Inc. Action Potential: Hyperpolarization Potassium gates remain open, causing an excessive efflux of K + This efflux causes hyperpolarization of the membrane The neuron is insensitive to stimulus and depolarization during this time Sodium channels start to reset – opening the inactivation channels and closing the activation gates

24. Copyright © 2010 Pearson Education, Inc. Action Potential: Role of the Sodium-Potassium Pump Repolarization restores the resting electrical conditions of the neuron Does not restore the resting ionic conditions Ionic redistribution back to resting conditions is restored by the sodium-potassium pump (what type of transport mechanism?)

25. Copyright © 2010 Pearson Education, Inc. Propagation of an Action Potential Na + influx causes an area of the axonal membrane to depolarize Local currents occur Na + channels toward the point of origin are inactivated and not affected by the local currents Local currents affect adjacent areas in the forward direction Depolarization opens voltage-gated channels and triggers an AP Repolarization wave follows the depolarization wave (Fig. 11.12 shows the propagation process in unmyelinated axons.)

26. Copyright © 2010 Pearson Education, Inc. Coding for Stimulus Intensity All action potentials are alike and are independent of stimulus intensity Strong stimuli can generate an action potential more often in a given time than weaker stimuli The CNS determines stimulus intensity by the frequency of impulse transmission

27. Copyright © 2010 Pearson Education, Inc. Absolute Refractory Period When the sodium channels are open, the neuron can not respond to another stimulus, no matter how strong it is Time from the opening of the Na + activation gates until the closing of inactivation gates The absolute refractory period: Prevents the neuron from generating an action potential Ensures that each action potential is separate (why is that important?) Enforces one-way transmission of nerve impulses PLAY InterActive Physiology ®: Nervous System I: The Action Potential, page 14

28. Copyright © 2010 Pearson Education, Inc. Relative Refractory Period During this period the axon threshold is elevated – (what does that mean?) The interval following the absolute refractory period when: Sodium gates are closed Potassium gates are open Repolarization is occurring PLAY InterActive Physiology ®: Nervous System I: The Action Potential, page 15

29. Copyright © 2010 Pearson Education, Inc. Conduction Velocities of Axons Conduction velocities vary widely among neurons Rate of impulse propagation is determined by: Axon diameter – the larger the diameter, the faster the impulse (effect less dramatic than myelination) Larger diameter fibers have less resistance to local current flow and have faster impulse conduction Presence of a myelin sheath – myelination dramatically increases impulse speed (will be discussed later) PLAY InterActive Physiology ®: Nervous System I: Action Potential, page 17

30. Copyright © 2010 Pearson Education, Inc. Axons types Axons are classified into 3 groups according to their relationships among the diameter, myelination and propagations speed: Type A – largest axons and myelinated. Speed is up to 150meters/second (~300mph!!!) Carry information about position, balance, touch and pressure sensation to the CNS Motor neurons that control skeletal muscle movement Type B and C are autonomic fibers Type B – smaller myelinated with an average propagation speed of 15m/s (30 mph) Type C – unmyelinated with propagation speed of 1m/s (2 mph) Type B and C carry information about temperature, pain and general touch sensations to the CNS Carry motor signals to smooth and cardiac muscles and glands

31. Copyright © 2010 Pearson Education, Inc. Saltatory Conduction (saltare – to leap) Current passes through a myelinated axon only at the nodes of Ranvier Voltage-gated Na + channels are concentrated at these nodes Action potentials are triggered only at the nodes and jump from one node to the next Much faster than conduction along unmyelinated axons

32. Copyright © 2010 Pearson Education, Inc. http://fourier.eng.hmc.edu/e180/handouts/figures/actionpotentialtransmission.gif

33. Copyright © 2010 Pearson Education, Inc. Multiple Sclerosis (MS) An autoimmune disease that mainly affects young adults Symptoms: visual disturbances, weakness, loss of muscular control, speech disturbances, and urinary incontinence Myelin sheaths in the CNS gradually destroyed Shunting and short-circuiting of nerve impulses occurs Impulse conduction slows and eventually ceases

34. Copyright © 2010 Pearson Education, Inc. Synapses A junction that mediates information transfer from one neuron: To another neuron To an effector cell Presynaptic neuron – conducts impulses toward the synapse – information sender Postsynaptic neuron – transmits impulses away from the synapse – information receiver

35. Copyright © 2010 Pearson Education, Inc. Electrical Synapses Are less common than chemical synapses Correspond to gap junctions found in other cell types Contain protein channels that connect the cells and allow ions and small molecules to flow from one cell to the other. Neurons that are joined together with electrical synapse are called - electrically coupled Transmission is fast Ability to synchronize several neurons together

36. Copyright © 2010 Pearson Education, Inc. Electrical Synapses More abundant in the embryo than in the adult (when neurons form connection with one another) Some electrical synapse in the embryo are replaced with chemical ones in the adult Have a role in the CNS in: Arousal from sleep Mental attention Emotions and memory Ion and water homeostasis PLAY InterActive Physiology ®: Nervous System II: Anatomy Review, page 6

37. Copyright © 2010 Pearson Education, Inc. Chemical Synapses Specialized for the release and reception of neurotransmitters (NT) Typically composed of two parts: Axonal terminal of the presynaptic neuron, which contains synaptic vesicles (containing the NT) Receptor region on the dendrite(s) or soma of the postsynaptic neuron PLAY InterActive Physiology ®: Nervous System II: Anatomy Review, page 7

38. Copyright © 2010 Pearson Education, Inc. Synaptic Cleft Fluid-filled space separating the presynaptic and postsynaptic neurons (30-50 nm wide) Prevents nerve impulses from directly passing from one neuron to the next Transmission across the synaptic cleft: Is a chemical event (as opposed to an electrical one) Ensures unidirectional communication between neurons (why?) PLAY InterActive Physiology ®: Nervous System II: Anatomy Review, page 8

39. Copyright © 2010 Pearson Education, Inc. Synaptic Cleft: Information Transfer Nerve impulses reach the axonal terminal of the presynaptic neuron and open voltage-gated Ca 2+ channels Ca 2+ enters the axonal terminal from the interstitial fluid. The Ca 2+ acts as intracellular messenger and promote the fusion of the vesicles with the axon membrane Neurotransmitter is released into the synaptic cleft via exocytosis in response to synaptotagmin (a Ca binding protein in the vescicle that might be part of exocytosis process) Ca 2+ is either taken by the mitochondria or ejected by active Ca 2+ pump (the trigger to this is unknown) Neurotransmitter crosses the synaptic cleft and binds to receptors on the postsynaptic neuron Postsynaptic membrane permeability changes (channels are open – chemically-gated channels), causing an excitatory or inhibitory effect

40. Copyright © 2010 Pearson Education, Inc. Termination of Neurotransmitter Effects As long as the NT is bound to the postsynaptic receptor it: Produces a continuous postsynaptic effect on permeability Blocks reception of additional “messages” They must be removed from its receptor Removal of neurotransmitters occurs when they: Are degraded by enzymes on the postsynaptic membrane or in the synapse Are reabsorbed by astrocytes or the presynaptic terminals Diffuse away from the synaptic cleft

41. Copyright © 2010 Pearson Education, Inc. Postsynaptic Potentials Receptors on the postsynaptic specialized in opening chemical-gated channels These channels are relatively insensitive to changes in the membrane potential That results in the inability of these channels to become self-generating Neurotransmitter receptor generate graded potential that depends on the amount of NT released

42. Copyright © 2010 Pearson Education, Inc. Postsynaptic Potentials Neurotransmitter receptors mediate changes in membrane potential according to: The amount of neurotransmitter released The amount of time the neurotransmitter is bound to receptors The two types of postsynaptic potentials are: EPSP – excitatory postsynaptic potentials IPSP – inhibitory postsynaptic potentials PLAY InterActive Physiology ®: Nervous System II: Synaptic Transmission, pages 7–12

43. Copyright © 2010 Pearson Education, Inc. Excitatory Postsynaptic Potentials EPSPs are graded potentials that can initiate an action potential in an axon Use a single type of chemically-gated ion channels that allows Na + and K + flow in opposite directions at the same time Electrochemical gradient for sodium is much steeper than that for potassium Sodium influx is greater than potassium efflux That will result in increased sodium concentration inside and depolarization

44. Copyright © 2010 Pearson Education, Inc. Excitatory Postsynaptic Potentials If enough NT are bound to the postsynaptic receptors, depolarization can reach 0 mV which is beyond axon threshold (-50mV) Postsynaptic membranes do not generate action potentials but its role is to generate EPSP that will trigger AP distally at the axon hillock. EPSP often travel all the way to the axon hillock (although decline with distance)

45. Copyright © 2010 Pearson Education, Inc. Inhibitory Synapses and IPSPs Neurotransmitter binding to a receptor at inhibitory synapses: Causes the membrane to become more permeable to potassium and chloride ions (causing hyperpolarization) Leaves the charge on the inner surface negative Reduces the postsynaptic neuron’s ability to produce an action potential

46. Copyright © 2010 Pearson Education, Inc. Integration: Summation A single EPSP cannot induce an action potential EPSPs can summate to reach threshold IPSPs can also summate with EPSPs, canceling each other out

47. Copyright © 2010 Pearson Education, Inc. Integration: Summation Temporal summation One or more presynaptic neurons transmit impulses in rapid- fire order presynaptic neurons transmit impulses in rapid-fire order first impulse produce small EPSP and the second arrives before the first disappears Spatial summation Postsynaptic neuron is stimulated by a large number of terminals at the same time

48. Copyright © 2010 Pearson Education, Inc. Summation IPSPs can also summate both temporally and spatially Most neuron receive both excitatory and inhibitory inputs from thousands of other neurons The axon hillock of the neuron keeps “records” of all signals – act as neural integrators EPSP summate with IPSP and depending on who dominate, that will be the effect on the cell. Partially depolarized neurons are said to be facilitated – more easily depolarized by the next stimulus

49. Copyright © 2010 Pearson Education, Inc. Table 11.1.1

50. Copyright © 2010 Pearson Education, Inc. Neurotransmitters The way neurons communicate with post-synaptic cells. NT are considered paracrine agents Most neurons make two or more neurotransmitters, which are released at different stimulation frequencies 50 or more neurotransmitters have been identified Classified by chemical structure and by function

51. Copyright © 2010 Pearson Education, Inc. Chemical Neurotransmitters Acetylcholine (ACh) – neuro-muscular junction, ANS Biogenic amines – substance produced by life processes. It may be either constituents, or secretions, of plants or animals (coal, oil, pearls etc). Example Catecholamines – dopamine, norepinephrine (NE), and epinephrine Amino acids - GABA – Gamma (  )-aminobutyric acid, Glycine, Aspartate, Glutamate (only in CNS) Peptides Novel messengers: ATP and dissolved gases NO and CO

52. Copyright © 2010 Pearson Education, Inc. Functional Classification of Neurotransmitters Two classifications: excitatory and inhibitory Excitatory neurotransmitters cause depolarizations (e.g., glutamate) Inhibitory neurotransmitters cause hyperpolarizations (e.g., GABA and glycine)

53. Copyright © 2010 Pearson Education, Inc. One NT – more than one receptor type The same NT released in different locations may have a different influence on the effectors (inhibitory/ excitatory) This leads to the conclusion that there are different subtypes of receptors that can react with the same NT

54. Copyright © 2010 Pearson Education, Inc. The effect of neurotransmitter on the postsynaptic membrane depends on the properties of the receptor !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!

55. Copyright © 2010 Pearson Education, Inc. Neurotransmitter Receptor Mechanisms Direct: neurotransmitters that open ion channels Promote rapid responses Examples: ACh and amino acids Indirect: neurotransmitters that act through second messengers Promote long-lasting effects Examples: biogenic amines, peptides, and dissolved gases PLAY InterActive Physiology ®: Nervous System II: Synaptic Transmission

56. Copyright © 2010 Pearson Education, Inc. Channel-Linked Receptors Composed of integral membrane protein Mediate direct neurotransmitter action Action is immediate, brief, simple, and highly localized Ligand binds the receptor, and ions enter the cells Excitatory receptors depolarize membranes Inhibitory receptors hyperpolarize membranes

57. Copyright © 2010 Pearson Education, Inc. Direct effect – receptors are part of the ion channel

58. Copyright © 2010 Pearson Education, Inc. G Protein-Linked Receptors Responses are indirect, slow, complex, prolonged, and often diffuse These receptors are transmembrane protein complexes Examples: muscarinic ACh receptors, neuropeptides, and those that bind biogenic amines

59. Copyright © 2010 Pearson Education, Inc. Indirect effect – through G-protein and 2 nd messenger

60. Copyright © 2010 Pearson Education, Inc. Neural Integration More synapses a neuron has the greater its information-processing capability cells in cerebral cortex with 40,000 synapses cerebral cortex estimated to contain 100 trillion synapses Chemical synapses are decision-making components of the nervous system ability to process, store and recall information is due to neural integration Based on types of postsynaptic potentials produced by neurotransmitters Millions of neurons in the CNS are organized in neuronal pools – functional groups that: Integrate incoming information Forward the processed information

61. Copyright © 2010 Pearson Education, Inc. Neural pools Neural pool neurons that share specific function Groups of neurons that influence each other’s activities Simple pool Consist of input fibers (presynaptic neurons) and output fibers (postsynaptic neurons). Postsynaptic fibers Discharge zone – neurons most closely associated with the incoming fiber – most likely to generate impulses Facilitated zone – neurons farther away from incoming fiber

62. Copyright © 2010 Pearson Education, Inc. Neural Pools and Circuits In discharge zone, a single cell can produce firing Output neurons in discharge zone form sufficient synapses with a single input neuron to discharge or fire when that input neuron fires. in facilitated zone, single cell can only make it easier for the postsynaptic cell to fire Output neurons in facilitation zone do not form enough synapses with that input fiber and will not discharge in response to that input fiber, but will be brought closer to threshold for firing (facilitation).

63. Copyright © 2010 Pearson Education, Inc. Types of Circuits in Neuronal Pools Divergent – one incoming fiber stimulates increasing number of fibers: Amplification - Signal spreads to an increasing number of neurons as it moves through successive orders of a neuronal pathway. Example - a signal from a single motor cortex neuron can excite 10,000 muscle fibers. Divergence into multiple tracts - A signal can split and go to two different destinations within the nervous system. Example - sensory information from the spinal cord splits and goes to cerebellum and to cerebral cortex. Figure 11.24a, b

64. Copyright © 2010 Pearson Education, Inc. Types of Circuits in Neuronal Pools Convergent – opposite of divergent circuits, resulting in either strong stimulation or inhibition in both sensory and motor systems The pool receives inputs from several presynaptic neurons The pool has a concentrating (funneling) effect Explains different stimuli that have the same effect. Figure 11.24c, d

65. Copyright © 2010 Pearson Education, Inc. Types of Circuits in Neuronal Pools Reverberating/oscillating – incoming signal travels along chain of neurons containing collateral synapses with previous neurons in the chain Uses positive feedback within a neuronal circuit to re-excite the input of the same circuit. Initial stimulus may only last for one msec but output will last for many msec to minutes. Circuit is eventually stopped by progressive synaptic fatigue or by inhibitory circuits This gives a continuous signal involved in rhythmic activities (sleep-awake cycle, breathing) Figure 11.24e

66. Copyright © 2010 Pearson Education, Inc. Types of Circuits in Neuronal Pools Parallel after-discharge – incoming neurons stimulate several neurons in parallel arrays that stimulate a common output cell Example – precise activity (math calculation) Figure 11.24f