The axon and the nerve impulse, Generation and propagation of the nerve impulse, Ionic channels, Synaptic transmission.

Transcription

1 The axon and the nerve impulse, Generation and propagation of the nerve impulse, Ionic channels, Synaptic transmission Mitesh Shrestha

2 Structure of the neuron the neuron consists of: the cell body, or perikaryon (contains the nucleus and the main concentration of organelles the dendrites (their number varies in a great range, theoretically from one to several hundreds; they are usually short and conduct impulses to the perikaryon the axon (neurite) - it is mostly very long and always single, it conducts the impulses away from respective cell (in the periphery the axons /in some neurone also dendrites/ run gathered together in groups termed as nerves) twig-like branchings or terminal arborizations - the telodendria, which touch the perikarya, dendrites or axons of one or more neurons in sites called synapses

3 Functional organization of the neuron functionally, three parts on each neurone are distinguished: reception part membranes of the all dendrites and cell body of the neurone synaptic potential transmission part the initial segment and axon of the neurone generation and propagation of nerve impulses secretion part - all axonal endings (presynaptic knobs) of respective neurone release od neurotransmitters

4 The Cells of the Nervous System The human nervous system is comprised of two kinds of cells: Neurons Glia The human brain contains approximately 100 billion individual neurons. Behavior depends upon the communication between neurons.

5 Figure : Estimated numbers of neurons in humans.

6 Figure: Neurons, stained to appear dark. Fig. 2-4, p. 32

7 The Cells of the Nervous System Like other cells in the body, neurons contain the following structures: Membrane Nucleus Mitochondria Ribosomes Endoplasmic reticulum

8 Fig. 2-2, p. 31

9 The Cells of the Nervous System The membrane refers to the structure that separates the inside of the cell from the outside environment. The nucleus refers to the structure that contains the chromosomes. The mitochondria are the strucures that perform metabolic activities and provides energy that the cells requires. Ribosomes are the sites at which the cell synthesizes new protein molecules

10 The Cells of the Nervous System All neurons have the following major components: Dendrites. Soma/ cell body. Axon. Presynaptic terminals.

11 The Cells of the Nervous System Dendrites- branching fibers with a surface lined with synaptic receptors responsible for bringing in information from other neurons. Some dendrites also contain dendritic spines that further branch out and increase the surface area of the dendrite.

12 Fig. 2-7, p. 33

13 The Cells of the Nervous System Soma - contains the nucleus, mitochondria, ribosomes, and other structures found in other cells. Also responsible for the metabolic work of the neuron.

14 The Cells of the Nervous System Axon - thin fiber of a neuron responsible for transmitting nerve impulses away to other neurons, glands, or muscles. Some neurons are covered with an insulating material called the myelin sheath with interruptions in the sheath known as nodes of Ranvier.

15 The Cells of the Nervous System Presynaptic terminals refer to the end points of an axon responsible for releasing chemicals to communicate with other neurons.

16 The Cells of the Nervous System Terms used to describe the neuron include the following: Afferent axon - refers to bringing information into a structure. Efferent axon - refers to carrying information away from a structure. Interneurons or Intrinsic neurons are those whose dendrites and axons are completely contained within a structure.

17 Figure: Cell structures and axons. Fig. 2-8, p. 34

18 The Cells of the Nervous System Neurons vary in size, shape, and function. The shape of a neuron determines it connection with other neurons and its connections with other neurons. The function is closely related to the shape of a neuron. Example: Pukinje cells of the cerebellum branch extremely widely within a single plane

19 Figure: The diverse shapes of neurons. Fig. 2-9, p. 34

20 The Cells of the Nervous System Glia are the other major component of the nervous system and include the following: Astrocytes helps synchronize the activity of the axon by wrapping around the presynaptic terminal and taking up chemicals released by the axon. Microglia - remove waste material and other microorganisms that could prove harmful to the neuron.

21 Figure: Shapes of some glia cells. Fig. 2-10, p. 35

22 Figure : How an astrocyte synchronizes associated axons. Branches of the astrocyte (in the center) surround the presynaptic terminals of related axons. If a few of them are active at once, the astrocyte absorbs some of the chemicals they release. It then temporarily inhibits all the axons to which it is connected. When the inhibition ceases, all of the axons are primed to respond again in synchrony. (Source: Based on Antanitus, 1998) Fig. 2-11, p. 36

23 The Cells of the Nervous System (Types of glia continued) Oligdendrocytes & Schwann cells- build the myelin sheath that surrounds the axon of some neurons. Radial glia- guide the migration of neurons and the growth of their axons and dendrites during embryonic development.

24 The Cells of the Nervous System The blood-brain barrier is a mechanism that surrounds the brain and blocks most chemicals from entering. Our immune system destroys damaged or infected cells throughout the body. Because neurons in the brain generally do not regenerate, it is vitally important for the blood brain barrier to block incoming viruses, bacteria or other harmful material from entering.

25 Figure: The blood-brain barrier. Most large molecules and electrically charged molecules cannot cross from the blood to the brain. A few small, uncharged molecules such as O2 and CO2 cross easily; so can certain fatsoluble molecules. Active transport systems pump glucose and amino acids across the membrane.

26 Cells and membrane potentials All animal cells generate a small voltage across their membranes This is because there is a large amount of small organic molecules in the cytoplasm To balance this, animal cell pump Na + out of the cells This regulates osmosis but it leaves a large number of organic molecules These are overall negatively changed (anions) in the cytoplasm Thus the cell has a potential difference (voltage) across its membrane

27 The Nerve Impulse.

28 The Nerve Impulse A nerve impulse is the electrical message that is transmitted down the axon of a neuron. The impulse does not travel directly down the axon but is regenerated at points along the axon. The speed of nerve impulses ranges from approximately 1 m/s to 100 m/s.

29 The Nerve Impulse The resting potential of a neuron refers to the state of the neuron prior to the sending of a nerve impulse. The membrane of a neuron maintains an electrical gradient which is a difference in the electrical charge inside and outside of the cell.

30 The Neuron at Rest The plasma membrane of neurons contains many active Na-K-ATPase pumps. These pumps shuttle Na+ out of the neuron and K+ into the neuron when ATP is hydrolyzed. Three Na+ are pumped out of the neuron at a time and two K+ ions are pumped in

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32 This creates a concentration gradient for Na+. As Na+ accumulates on the outside of the neuron, it tends to leak back in. Na+ must pass through proteins channels to leak back through the hydrophobic plasma membrane. These channels restrict the amount of Na+ that can leak back in. This maintains a strong positive charge on the outside of the neuron

33 The K+ inside the neuron also tends to follow its concentration gradient and leak out of the cell. The protein channels allow K+ to leak out of the cell more easily. As a result of this movement in Na+ and K+ ions, a net positive charge builds up outside the neuron and a net negative charge builds up inside.

34 This difference in charge between the outside and the inside of the neuron is called the Resting Potential. The resting potential in most neurons is 70 mv. When the neuron is at rest, it is polarized

35 The Nerve Impulse The membrane is selectively permeable, allowing some chemicals to pass more freely than others. Sodium, potassium, calcium, and chloride pass through channels in the membrane. When the membrane is at rest: Sodium channels are closed. Potassium channels are partially closed allowing the slow passage of sodium.

36 Resting Potential Experiments have been carried out using Giant Squid axons These are large enough to have microelectodes inserted into then to measure changes in electrical charge. One electrode is inserted into the axon and one is placed on the outside of the cell membrane

37 Experiments on the neuron of a giant Ion squid Concentration /mmol kg -1 water Axoplasm (the cytoplasm in an axon) Blood plasma Sea water K Na Cl Organic anions (-ve ions) Paul Billiet ODWS

38 Resting Potential

39 Maintaining the Resting Potential Cation pumps (Na pumps) maintain active transport of K + ions in and Na + out of the neurone 3 Na + ions are pumped out at the same time 2 K+ ions are pumped in This is done by the Sodium Potassium ATPase pump

40 An Action Potential Action Potential An action potential is produced when membrane of neuron stimulated, the charge is reversed: The inside of the axon was -70 mv and this changes to +40 mv and membrane is said to be depolarized

41 An Action Potential A nerve impulse can be initiated by mechanical, chemical, thermal or electrical stimulation Experiment show that when a small electrical current is applied to the axon the resting potential changes from 70 mv to + 40 mv This change in potential is called the action potential

42 Initiation of the Action Potential A change in the environment ( pressure, heat,sound, light) is detected by the receptor and changes the shape of the channel proteins in part of the neuron usually the dendrites. The Na+ channels open completely and Na+ ions flood into the neuron. The K+ channel close completely at the same time and K+ ions can no longer leak out of the neuron in that particular area.

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44 +35 mv 0-55 More Na + channels open Na + floods into neuron Na + voltagegated channels open Threshold -70 Time Resting potential Action potential 2008 Paul Billiet ODWS

45 The interior of the neuron in that area becomes positive relative to the outside of the neuron. This depolarization causes the electrical potential to change from 70 mv to + 40 mv The Na+ channels remain open for about 0.5 milliseconds then they close as the proteins enter an inactive state. The total change between the resting state (-70 mv) and the peak positive voltage ( +40mV) is the action potential ( about 110 mv)

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47 The spike in voltage causes the K+ pumps to open completely and K+ ions rush out of the neuron. The inside becomes negative again. This is repolarization. So many K+ ions get out that the charge goes below the resting potential. While the neuron is in this state it cannot react to additional stimuli. The Refractory period lasts from 0.5 to 2 milliseconds. During this time, the Na-K-ATPase pump reestablishes the resting potential.

48 +35 0 Na + channels close and K + channels open, K + floods out of neurone mv -55 Threshold -70 Resting potential Time Action potential Resting potential 2008 Paul Billiet ODWS

49 Hyperpolarisation The membrane potential falls below the resting potential of 70mV It is said to be hyperpolarised Gradually active pumping of the ions (K + in and Na + out) restores the resting potential During this period no impulses can pass along that part of the membrane This is called the refractory period 2008 Paul Billiet ODWS

50 +35 0 Hyperpolarisation of the membrane mv -55 Active pumping of Na + out and K + in during the refractory period Threshold Paul Billiet ODWS Resting potential Time Action potential Resting potential

51 Transmission of the impulse The stimulus induces depolarization in a very small part of the neuron, at the dendrites. The sequence of depolarization and repolarization generates a small electrical current in this localized area. The current affects the nearby protein channels for Na+ and causes them to open.

52 When the adjacent channels open, Na+ions flood into that area of the neuron and an action potential occurs. This in turn will affect the areas next to it and the impulse passes along the entire neuron. The electric current passes outward over the membrane in all directions BUT the area to one side is still in the refractory period and is not sensitive to the current. Therefore the impulse moves from the dendrites toward the axon.

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54 Threshold stimulus Action potentials occur only when the membrane in stimulated (depolarized) enough so that sodium channels open completely. The minimum stimulus needed to achieve an action potential is called the threshold stimulus. If the membrane potential reaches the threshold potential (generally 5-15 mv less negative than the resting potential), the voltage-regulated sodium channels all open. Sodium ions rapidly diffuse inward, & depolarization occurs.

55 All-or-None Law Action Potentials occur maximally or not at all. In other words, there's no such thing as a partial or weak action potential. Either the threshold potential is reached and an action potential occurs, or it isn't reached and no action potential occurs. However, different neurons have different densities of Na+ channels and therefore have different APs

56 The AP remains constant as it travels down the neuron. Its amplitude is always the same because it corresponds to wide open Na+ channels. The frequency of the AP can change.

57 Conduction Velocity impulses typically travel along neurons at a speed of anywhere from 1 to 120 meters per second the speed of conduction can be influenced by: The diameter of a fiber. Velocity increases as diameter increases. Temperature. As temperature increases, the velocity increases. Axons of birds and mammals can be very small because of the high body temperature. the presence or absence of myelin.

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59 Neurons with myelin (or myelinated neurons) conduct impulses much faster than those without myelin. Because fat (myelin) acts as an insulator, membrane coated with myelin will not conduct an impulse. So, in a myelinated neuron, action potentials only occur along the nodes and, therefore, impulses 'jump' over the areas of myelin - going from node to node in a process called saltatory conduction (the word saltatory means 'jumping')

60 Saltatory conduction Used to describe jumping of the action potential from node to node. Provides rapid conduction of impulses Conserves energy for the cell Multiple sclerosis is a disease in which the myelin sheath is destroyed and associated with poor muscle coordination.

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62 The Refractory Period Absolute refractory period: This lasts for about 1 msec during which no impulses can be propagated however intense the stimulus Relative refractory period: This lasts for about 5 msec during which new impulses can only be generated if the stimulus is more intense than the normal threshold

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64 The refractory Period The refractory period ensures that: Impulses can flow in only one direction as the region behind the impulse cannot be depolarised It limits the frequency at which successive impulses can pass along an axon.

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66 The Nerve Impulse Not all neurons have lengthy axons. Local neurons have short axons, exchange information with only close neighbors, and do not produce action potentials. When stimulated, local neurons produce graded potentials which are membrane potentials that vary in magnitude and do not follow the all-or-none law,. A local neuron depolarizes or hyperpolarizes in proportion to the stimulation.

67 Formation of an action potential The formation of an action potential can be divided into five steps. (1) A stimulus from a sensory cell or another neuron causes the target cell to depolarize toward the threshold potential. (2) If the threshold of excitation is reached, all Na+ channels open and the membrane depolarizes. (3) At the peak action potential, K+ channels open and K+ begins to leave the cell. At the same time, Na+ channels close. (4) The membrane becomes hyperpolarized as K+ ions continue to leave the cell. The hyperpolarized membrane is in a refractory period and cannot fire. (5) The K+ channels close and the Na+/K+ transporter restores the resting potential.

68 Summary of Neural Impulse

69 Neurotransmission / Synaptic transmission the process by which signaling molecules called neurotransmitters are released by a neuron (the presynaptic neuron), and bind to and activate the receptors of another neuron (the postsynaptic neuron). Essential for the process of communication between two neurons. Synaptic transmission relies on: the availability of the neurotransmitter; the release of the neurotransmitter by exocytosis; the binding of the postsynaptic receptor by the neurotransmitter; the functional response of the postsynaptic cell; and the subsequent removal or deactivation of the neurotransmitter.

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71 Synaptic transmission: communication between neurons

72 Two principal kinds of synapses: electrical and chemical

73 Gap junctions are formed where hexameric pores called connexons connect with one between cells

74 Chemical synapses: the predominant means of communication between neurons

75 Stages in neurotransmission at the synapse Synthesis of the neurotransmitter. This can take place in the cell body, in the axon, or in the axon terminal. Storage of the neurotransmitter in storage granules or vesicles in the axon terminal. Calcium enters the axon terminal during an action potential, causing release of the neurotransmitter into the synaptic cleft. After its release, the transmitter binds to and activates a receptor in the postsynaptic membrane. Deactivation of the neurotransmitter. The neurotransmitter is either destroyed enzymatically, or taken back into the terminal from which it came, where it can be reused, or degraded and removed.

76 Criteria that define a neurotransmitter: 1. Must be present at presynaptic terminal 2. Must be released by depolarization, Ca ++ -dependent 3. Specific receptors must be present

77 Neurotransmitters Catecholamine Neurotransmitters Derived from amino acid tyrosine Dopamine [Parkinson s], norepinephrine, epinephrine Amine Neurotransmitters acetylcholine, histamine, serotonin Amino Acids aspartic acid, GABA, glutamic acid, glycine Polypeptides Include many which also function as hormones endorphins

78 Transmission of signals based on MULTIPLE STIMULI combined excitatory & inhibitory neurons Inhibition in Pre-synaptic neuron Ca + channels blocked stops release of neurotransmitter Inhibition in Post-synaptic neuron opens Cl- channels makes interior more [-] increase permeability of K + ions makes interior more [-]

79 Neurotransmitters may be either small molecules or peptides Mechanisms and sites of synthesis are different Small molecule transmitters are synthesized at terminals, packaged into small clear-core vesicles (often referred to as synaptic vesicles Peptides, or neuropeptides are synthesized in the endoplasmic reticulum and transported to the synapse, sometimes they are processed along the way. Neuropeptides are packaged in large dense-core vesicles

80 The synaptic vesicle cycle

81 Convergence and divergence Neurotransmission implies both a convergence and a divergence of information. First one neuron is influenced by many others, resulting in a convergence of input. When the neuron fires, the signal is sent to many other neurons, resulting in a divergence of output. Many other neurons are influenced by this neuron.