Lecture 3 (Oct 5 th ): NEURONS AND NERVE IMPULSES Lecture Outline

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Lecture 3 (Oct 5 th ): NEURONS AND NERVE IMPULSES Lecture Outline 1) CNS vs. PNS 2) Structure of Neurons parts of a neuron: soma, dendrites, axons 3) Glial Cells 4) Mitosis and Regeneration in Neurons 5) Neuronal Communication 6) The Nerve Signal (Electrical) - A Neuron at Rest - Graded Potentials and Action Potentials (REALLY FAST!) 7) Multiple Sclerosis Blood Brain Barrier (you learn from book, just the very basics)

Things I want to clarify from last lecture 1) TTT in female song birds -> hypothalamic nuclei increase in size -> female bird sings. This is causal, but we cannot be sure the cause is not TTT 2) Why did I say we never know who the father is?

THE NERVOUS SYSTEM 1) Central Nervous System (CNS): Brain and Spinal Cord 2) Peripheral Nervous System (PNS): The Rest Two types of cells in the Nervous System: 1) Neurons (100 billion, 10 11 ): communicate through electrical signals 2) Glia (10 12, but 1/10th the size of neurons) form the myelin sheath of neurons will come back to later today

applethe NEURON Components common to all cells of the body: cytoplasm, nucleus membrane H 2 0, 0 2, C0 2, urea pass freely across membrane Large or Electrically charged molecules do NOT -> Need ionic channels for: K +, Na +, Cl - mitochondria (energy from metabolism) ribosomes (synthesis of new proteins) lysosomes (break things down -> recycle) Golgi complex (secretion of waste)

How Neurons are like other cells:

Node of Ranvier synapse Components unique to NEURONS: soma (sometimes called cell body ) dendrites (one or many): receive signals axon: sends electrical signal to next neuron presynaptic ( before the synapse ) terminals synapse myelin sheath (glia): Not found in invertebrates nodes of Ranvier (will come back to later today)

GLIAL CELLS (support cells) 1) Form the MYELIN SHEATH CNS: Oligodendrocytes PNS: Schwann Cells 2) Microglia & Astrocytes (CNS) remove waste material, dead neurons A student told me not true for Astrocytes 3) Radial Glia direct neurons during development

NEURON: Mitosis (Make New Neurons) and Regeneration (Repair Injured Neurons) MITOSIS: After development, neurons in both the CNS and PNS lose their ability to undergo mitosis which is a bummer if there is an injury (e.g., stroke)! Why is it this way? (we ll come back to in a couple of slides) Exceptions: Some neurons that DO undergo Mitosis (adults) 1) Olfactory neurons 2) Isolated parts of bird, rodent and PRIMATE brain (e.g., hippocampus involved in memory) QUESTION: As we age don t brain cells die and are not replaced? (uh-oh!) No, they just shrink and are less functional. Phew!??!

And what about BRAIN CANCER? Isn t cancer when mitosis has gone wild??!! Well brain cancer is usually GLIA, not NEURONS Glial cells in both the CNS and PNS undergo mitosis.

REGENERATION: of cut AXONS in the PNS. not the CNS In PNS, there are mechanisms for creating collagen around the injury to act as a bridge for axons to grow along. Questions to Mother Nature: Why is there no regeneration in the CNS? Why is there no MITOSIS in adulthood, in both the CNS and PNS? (especially important to know for spinal cord injury)

Neural Communication PRESYNAPTIC POSTSYNAPTIC Node of Ranvier synapse Electrical signal sent from one neuron to the next (from the presynaptic -> postsynaptic neuron ), or muscle Neuromuscular Junction

PRESYNAPTIC POSTSYNAPTIC R R R R R synapse R R R R R Overview of Events: 1) Electrical signal starts in the presynaptic neuron and travels down the axon to the presynaptic terminals. 2) Causes release of neurotransmitter into the synapse 3) Neurotransmitter binds to receptors (R) on postsynaptic neuron s dendrites 4) Triggers an electrical signal in postsynaptic neuron, and so on.. MORE LATER TODAY AND NEXT LECTURE

Some Relative Terms about Neuronal Connections: 1) PRESYNAPTIC vs. POSTSYNAPTIC 2) AFFERENT vs. INTRINSIC vs. EFFERENT AFFERENT INTRINSIC EFFERENT STRUCTURE X

Speed of Transmission: electricity (electrons): 6 x 10 6 m/sec myelinated: 100 m/sec thick unmyelinated: 10 m/sec thin unmyelinated: 1 m/sec apple DEMO of the Nerve Impulse

How Do Electrical Signals Travel Along a Neuron? Let s Learn this as a Story What is a Membrane Potential? Voltage/Electrical Difference between IN and OUTside of neuron At REST : the Membrane Potential = -70 mv i.e., the inside of the neuron is more NEGATIVE than outside (large, negatively-charged molecules trapped inside!) - H 2 0, 0 2, C0 2, -> pass freely across cell membrane - Electrically Charged IONS : K + = Potassium Na + = Sodium also Cl - = Chloride (next lecture) can only cross membrane through ION CHANNELS (or pores )

- ION CHANNELS are SELECTIVE for different ions - ION CHANNELS are relatively OPEN or CLOSED depending on the VOLTAGE of membrane This is called a VOLTAGE-GATED Ion Channel At Rest (i.e., -70 mv): K + (and Cl - ) channels are OPEN - CONCENTRATION DIFFERENCE across MEMBRANE At Rest (i.e., -70mV): K + : Inside > Outside Na + : Outside > Inside

3 forces across membrane (red is what happens at -70 mv) 1) Na + /K + PUMP (K + in, Na + out), (not through ion channels!), relies on ATP 2) Electrical Gradient (K + in, Na + in) 3) Concentration Gradient (K + out, Na + in): diffusion http://highered.mheducation.com/sites/0072495855/student_view0/chapter2/ animation how_the_sodium_potassium_pump_works.html Remember, forces (2) and (3) want Na + to go IN, but WHY does Na + stay OUTside at REST (-70 mv)??? 1 3 2 OVERALL NEGATIVE IN HERE!

The Membrane Potential (Voltage) can CHANGE from 70mV = an electrical signal! (which then travels down the axon) Depolarization: membrane potential less negative (i.e., more +) How does the Membrane Potential get depolarized? (I mentioned this earlier today and we ll return to in the next lecture) -> Neurotransmitters bind to receptors on neuron Hey! What about the 1 st neuron in the chain? (Stimulus -> more on this in a few weeks) Hyperpolarization: membrane potential becomes more negative

Electrical signal travels along the axon: 1) Graded Potentials, or 2) Action Potential 1) Graded Potential: The strength of the depolarization diminishes (is graded ) over time and distance (as it travels down axon). This signal can only survive for a short distance along the axon. - Fine for short neurons (e.g., in the retina). 2) ACTION POTENTIAL Occurs if membrane depolarization gets to -55 mv = threshold Then, big depolarization signal (to +30 mv), which does not diminish as it travels down axon. ALL-OR-NONE,

What happens at -55 mv? (8 steps) Let s Go Through this FAST.. You go over it carefully later 1) Na + (Voltage-Gated) Channels (which were closed at -70 mv) start to OPEN 2) Na + ions rush INSIDE the neuron down the concentration and electrical gradient -> inside becomes even more positive (+), i.e., more depolarized -> therefore Na + channels open even more, etc. (positive feedback loop) 3) K + channels are also voltage-gated. Although already open in the resting state (-70 mv), K + open even more when the neuron becomes depolarized.

4) K + rushes OUT of the neuron Down the concentration gradient Hey, but what about the electrical gradient??? Concentration Grating beats Electrical Gradient And. once membrane potential is a POSITIVE number (+), K + also goes down the electrical gradient. (4) is what starts to make the inside of the neuron go back towards being negative! 5) So, Membrane potential heads back towards its resting state (i.e., -70 mv). 6) And, voltage-gated Na + (and K + ) channels start to close. 7) K + exit onsets more slowly and lasts longer than Na + entry. Therefore K + continues to leave the neuron, which hyperpolarizes the neuron briefly (more negative than 70mV)

8) After an action potential, the membrane potential is back to resting state (i.e., ~ -70 mv), but. Na + and K + concentrations (inside/outside) have changed and need to be put back! How? Na+/K+ pump! Na + OUT, K + IN

Nodes of Ranvier / Saltatory Conduction Myelin Sheath

Nodes of Ranvier / Saltatory Conduction What goes wrong in Multiple Sclerosis (MS)? Myelin Sheath 1) Early in development, when no myelin yet 2) Later, you develop myelin, and the ion channels underneath the myelin go away 3) MS: myelin gets destroyed by own immune system

BLOOD BRAIN BARRIER (BBB) purpose: keep out viruses, bacteria in CNS How the BBB works: - in all body parts, endothelial cells line the inside of blood vessels - in all body parts except the CNS, there exist gaps between these endothelial cells, so substances in the blood can move out of the blood vessels to the body parts - in the CNS, there are tight junctions between cells, which disallow this movement Fuel for the CNS (glucose and O 2 ) get through the BBB: - with an active transport system (glucose) - with diffusion (O 2 ). Drugs that that get through the BBB: Fat-soluble substances, e.g., heroin, nicotine, cannabinoids -> dissolve through fats of blood vessel walls