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Communication within the Nervous System The Cells that make us who we are How neurons communicate with one another 1 The Cells That Make Us Who We Are • How many are there? • Neurons: 100 billion • Make up 10% of brain volume • Glia: Many more! • Make up 90% of brain volume • Neurons: Jobs include • convey sensory information to the brain; • carry out operations involved in thought and feeling; 2 The Cells That Make Us Who We • Send commands out to the body. • Dendrites • Cell body or soma • Axons insulated with myelin (secreted by glia), with end terminals that release neurotransmitters from vesicles into the synapse Are Figure 2.3: Components of a Neuron 3 The Cells That Make Us Who We 4 The Cells That Make Us Who We Are Figure 2.4 a,b: The Three Shapes of Neurons •Unipolar neurons (a) •Bipolar neurons (b) •Multipolar neurons • Figure 2.3, previous slide 5 The Cells That Make Us Who We Are Table 2.1: The Three Types of Neurons Figure 2.4c: The Three Shapes of Neurons 6 The Cells That Make Us Who We Type Shape Description Motor neuron Multipolar Output to muscles/organs Sensory neuron Unipolar or Bipolar Input from receptors Interneuron Multipolar Within, axon 7 The Cells That Make Us Who We Are Figure 2.5: Composition of the Cell Membrane • Lipids • Heads attracted to water in and outside the cell, tails repelled by water • Creates a double-layer membrane • Proteins • Hold the cells together • Controls the environment in and around the cell 8 The Cells That Make Us Who We 9 The Neural Membrane • The neuron has a selectively-permeable membrane. • Water and gases pass freely through • Other substances are barred from entry. • Others pass through protein channels in the membrane under certain circumstances. • Polarization results from selective permeability of the membrane. • Polarization: difference in electrical charge between the inside and outside of the cell. 10 The Neural Membrane • This difference in electrical charge is referred to as a voltage. • A potential is any change in a membrane’s voltage. •The resting potential is the difference in charge between the inside and outside of the membrane of a neuron at rest. • Between -40 and -80 millivolts (mV) in different neurons. • A typical neuron’s resting potential is around -70 mV. • Caused by unequal distribution of ions on either side of the membrane. 11 The Neural Membrane • Outside contains mostly sodium (Na+) and chloride (Cl-) ions. • Inside contains mostly potassium (K+) ions and organic anions (A-). Figure 2.7: The Sodium-Potassium Pump •Sodium-potassium pump 12 The Neural Membrane • Moves 3 Na+ outside for every 2 K+ inside •Force of diffusion: • Ions flow from high to low concentration •Electrostatic pressure • Ions attracted to the opposite charge (+ to -), and repelled by the same charge (+ from +) 13 The Neural Membrane •Excitatory signals cause a partial hypopolarization (or depolarization), in a small area of the membrane. • The hypopolarization is caused by a change in ion balance, which also affects the adjacent membrane. • This spreading hypopolarization diminishes over distance, so it is often referred to as a local potential. •At the axon hillock, if hypopolarization reaches threshold (around -60 mV), an action potential will be triggered. 14 The Neural Membrane The Action Potential Depolarization is the change in the resting neuron’s polarity toward zero 15 The Neural Membrane +30 mV 0 mV Hypopolarized threshol d Resting Potential -70 mV -80 mV Hyperpolarize d 16 The Neural Membrane Figure 2.8a: The Action Potential 1. 2. 4. 5. Membrane depolarized past threshold through a series of graded potentials. Voltage-gated Na ions open, Na enters 3. Voltage-gated K channels open, K exits. K channels slowly close and membrane returns to resting potential. The Action Potential lasts about 1 millisecond 17 The Neural Membrane • Movement of action potentials down the axon is not a flow of ions but a chain of events... 18 The Neural Membrane depolarizing adjacent membrane areas which triggers another action potential. • When the action potential reaches the terminals it passes the message on to the next cell “in line”. • The local potential is a graded potential, but the action potential follows the all-or-none law. • Always occurs at full strength and doesn’t vary with stimulus intensity. • Nondecremental 19 The Neural Membrane • Message travels over long distances at the same amplitude • Rate Law: Firing rate of neuron proportional to stimulus intensity Absolute vs. Relative Refractory Period 20 The Neural Membrane +60 mV +20 mV -20 mV -60 mV Relative Refractory Period 0 1 2 3 4 5 Time between Action Potentials (ms) 6 7 21 The Cells That Make Us Who We Are Effects of Neurotoxins and Anesthetics •Neurotoxins affect ion channels involved in the action potential. • Tetrodotoxin blocks sodium channels. • Scorpion venom opens sodium channels, prolonging the action potential. •Beneficial drugs affect these ion channels as well. • Local anesthetics block sodium channels. 22 • General anesthetics work by opening potassium channels. •Optogenetics. • Modified ion channels that are triggered by light. Glial Cells Myelination, Axon diameter, and conduction speed • Myelin, secreted by glial cells, is a fatty tissue that surrounds axons, providing electrical insulation and support. • CNS: oligodendrocytes 23 • PNS: Schwann cells • Increases the conduction speed from 1 m/s to over 120 m/s. • Myelin gaps called nodes of Ranvier are where action potentials occur... i.e. where sodium ions enter the axon. • Transmission between nodes (under the myelin) is by local potential. • Saltatory conduction: the action potential “jumps” from node to node. • Multiple sclerosis is a disease in which myelin is destroyed, reducing conduction speed. • Axons with a larger diameter will conduct signals faster than axons with a smaller diameter. 24 Glial Cells Figure 2.9: Glial Cells Produce Myelin for Axons 25 26 Glial cells Figure 2.11: Astrocyte Density Correlates With Behavioral Complexity • Scaffolds for migrating neurons... guides new neurons in fetal development • Respond to injury and disease by removing debris. • Provide energy to neurons. • 7X more neural connections when glia are present 27 Glial Cells Figure 2.10: Glial Cells Increase the Number of Connections Between Neurons. 28 SOURCE: From “Synaptic Efficacy Enhanced by Glial Cells in vitro,” by F. W. Pfrieger and B. A. Barres, Science, 277, p. 1684. © 1997. Used by permission of the author. 29 How Neurons Communicate With One Another Figure 2.12: The Synapse Between a Presynaptic Neuron and a Postsynaptic Neuron 30 How Neurons Communicate With One Another •Synapse: connection between a neuron and another cell • Presynaptic neuron transmits the signal • Postsynaptic cell receives the signal • Synaptic cleft (gap) between the two 31 How Neurons Communicate With One Another Figure 2.13: Loewi’s Experiment Demonstrating Chemical How Neurons Communicate With One Another Transmission in Neurons • One of two methods: • Stimulated vagus nerve, slowed heart A • Stimulated accelerator nerve, sped up heart A. • Injected solution from heart A into heart B • Heart B rate changed to match in similar ways • Loewi’s conclusion • Heart uses chemical messengers, not action potentials, to change heart rate. Steps of the Synaptic Event 33 How Neurons Communicate With One Another 2+ 1. Action potential depolarizes pre-synaptic membrane, Ca2+ channels open and Ca enters cell 2. Neurotransmitter released into cleft 3. NT binds to post-synaptic receptors 4. Ionotropic receptor opens post-synaptic ion channels, changing Ca2+ EPSP Receptor Na+ 22 “Ionotropic effect” How Neurons Communicate With One Another the potential http://www.youtube.com/watch?v=http://www.yo Postsynaptic Receptor Types •Ionotropic receptors 35 How Neurons Communicate With One Another • cause ion channels to open, which • has a direct and rapid effect on the neuron. •Metabotropic receptors • open channels indirectly, • producing slower but longer-acting effects. •Synaptic transmission is much slower than axonal (electrical) transmission. How Neurons Communicate With One Another Excitatory & Inhibitory Postsynaptic Potentials •Activation of receptors on the postsynaptic cell has two possible effects on the membrane potential. • Hypopolarization creates an excitatory postsynaptic potential (EPSP). • An EPSP opens sodium channels. • This makes the postsynaptic neuron more likely to fire. • Hyperpolarization creates an inhibitory postsynaptic potential (IPSP). 37 How Neurons Communicate With One Another • An IPSP opens potassium or chloride channels or both. • This makes it less likely an action potential will occur. Postsynaptic Potentials are Graded •EPSPs and IPSPs are graded potentials. • Accumulate over a short time (temporal summation) • Combine inputs from different locations on dendrites and cell body (spatial summation) •The neuron acts as a(n) 38 How Neurons Communicate With One Another • Information integrator (summation) • Decision maker (excitatory and inhibitory inputs combine algebraically, fires when above threshold) • The Decision Point is the Axon Hillock, where the Axon joins the cell body / Soma. Figures 2.18 (left) & 2.17 (right): Temporal & Spatial Summation. 39 How Neurons Communicate With One Another 40 How Neurons Communicate With One Another Removal of Neurotransmitters and Drug Effects • Neurotransmitters must be removed to allow frequent responding and to prevent it from affecting nearby synapses. • Reuptake: the transmitter brought back into the terminals • Inactivation: enzymes break down the transmitter in the cleft • Drugs • Some mimic natural transmitters and stimulate receptors themselves (agonists) 41 How Neurons Communicate With One Another • Some block neurotransmitter receptors (antagonists) • Some enhance or reduce transmitter effects. For example: • Antidepressants block reuptake of serotonin (SSRIs) • Some prevent neurotransmitter inactivation (MAOIs) Regulation of Synaptic Activity • One regulatory process occurs in axoaxonic synapses • Presynaptic inhibition decreases the release of transmitter. • Presynaptic excitation increases the release of transmitter. • This regulation occurs by affecting calcium entry into the terminal. 42 How Neurons Communicate With One Another • Autoreceptors sense the amount of transmitter in the cleft and cause the presynaptic neuron to reduce excessive output. • Glial cells • prevent transmitter from spreading to other synapses; • absorb and recycle transmitter for the neuron’s reuse; • release glutamate to regulate presynaptic transmitter release. A Variety of Neurotransmitters Multiplies the Possible Synaptic Effects 43 How Neurons Communicate With One Another •Receptor subtypes add more complexity • Acetylcholine receptor has nicotine and muscarinic subtypes. •Neurons can release more than one chemical • One fast-acting plus one or more slower-acting neuropeptides • Two or more fast-acting transmitters • Excitatory & inhibitory transmitters at different synapses 44 How Neurons Communicate With One Another • Contradicts Dale’s principle that neurons can only release one neurotransmitter 45 How Neurons Communicate With Each Other Table 2.2b: Some Representative Neurotransmitters 46 Neurotransmitter Function Acetylcholine Transmitter at muscles; in brain, involved in learning, etc. Monoamines Serotonin Involved in mood, sleep and arousal, aggression, depression, obsessivecompulsive disorder, and alcoholism Dopamine Contributes to movement control and promotes reinforcing effects of food, sex, and abused drugs; involved in schizophrenia and Parkinson’s disease. Norepinephrine Released during stress. Neurotransmitter in the brain to increase arousal and attentiveness to events in the environment; involved in depression. Epinephrine A stress hormone related to norepinephrine; plays a minor role as a neurotransmitter in the brain. Amino Acids Glutamate The principal excitatory neurotransmitter in the brain and spinal cord. Vitally involved in learning and implicated in schizophrenia. 47 Gamma-aminobutyric acid (GABA) The predominant inhibitory neurotransmitter. Its receptors respond to alcohol and the class of tranquilizers called benzodiazepines. Deficiency in GABA or receptors is one cause of epilepsy. Glycine Inhibitory transmitter in the spinal cord and lower brain. The poison strychnine causes convulsions and death by affecting glycine activity. How Neurons Communicate With Each Other Table 2.2b: Some Representative Neurotransmitters 48 Neurotransmitter Function Neuropeptides Endorphins Neuromodulators that reduce pain and enhance reinforcement. Substance P Transmitter in neurons sensitive to pain. Neuropeptide Y Initiates eating and produces metabolic shifts. Gas Nitric Oxide One of two known gaseous transmitters, along with carbon monoxide. Can serve as a retrograde transmitter, influencing the presynaptic neuron’s release of neurotransmitter. Viagra enhances male erections by increasing nitric oxide’s ability to relax blood vessels and produce penile engorgement. How Neurons Communicate With One Another Neuronal Coding and Neural Networks 49 •Neuronal coding and neural networks add further complexity to neural processing. • Trains of neural impulses encode additional information in the intervals between spikes and length of bursts. • Some information is encoded by segregating it to specialized pathways known as “labeled lines.” • In the brain, information is integrated and processed in complex neural networks. •One way of studying these networks is to simulate their activity with computer-based artificial neural networks. 50 • Detecting cancer in a biopsy sample Figure 2.23: Image of White Matter Fiber Tracts 51 52 SOURCE: Courtesy of Jason Wolff. 53