0111.1220מבוא למדעי העצב הקורס יינתן בשנת הלימודים הראשונה שם מרכז הקורס :פרופ' אילנה לוטן שמות המורים המלמדים בקורס :פרופ' אילנה לוטן וכן ד"ר שרון ויס האחראית על העברת 3 סימולציות במהלך הקורס :סימולציית עצב חד סיבי ,סימולציה עצב רב סיבי ,סימולציית שריר הקורס יעסוק במנגנונים מולקולריים ותאיים שמהווים בסיס לפעילות של תאים אקסיטביליים ,מערכת העצבים ושריר השלד .הדגש הוא על מנגנונים של עוררות ) (excitabilityבאופן כללי ,תופעות חשמליות בנוירונים ותאי שריר ,עקרונות של העברה סינפטית ,ומנגנונים של התכווצות השריר. הפרקים הנלמדים בקורס כוללים: .1פוטנציאלים חשמליים בתאים אקסיטביליים – תעלות יוניות ,נשאים ומשאבות .2פוטנציאל פעולה -מנגנון יוני ,תקופה רפרקטורית ,הולכת פ"פ .3תעלות יוניות והמחלות הנובעות מתפקוד לקוי שלהן .4סינפסות חשמליות וכימיות – מורפולוגיה ועקרונות הפעולה ,סינפסת עצב-שריר .5תקציר על סינפסות וטרנסמיטרים במערכת העצבים המרכזית .6מבנה וחלבוני שריר השלד .7צימוד בין עוררות והתכווצות ,מנגנון וחוקי ההתכווצות ותכונות מכניות של שריר השלד. היקף הקורס 59 -שעות 35 ,שעות פרונטליות ,כ 5-6שעות שבועיות במשך חצי סמסטר (7 שבועות) ,ו 24שעות סימולציות מחשב ( 8שעות לכל תלמיד) פירוט סימולציות המחשב במהלך הקורס :סימולציה עצב חד סיבי ,סימולציה עצב רב סיבי וסימולצית שריר. הציון בקורס ייקבע על פי מבחן ודוחות סימולצית מחשב :עצב חד סיבי ,עצב רב סיבי וסימולצית שריר .תנאי מחייב לקבלת ציון עובר בקורס :קבלת ציון עובר בבחינה המסכמת. A. Physiology of the Neuron NEU 1. Define, and identify on a diagram of a motor neuron, the following regions: dendrites, axon, axon hillock, soma, and an axodendritic synapse. NEU 2. Define, and identify on a diagram of a primary sensory neuron, the following regions: receptor membrane, peripheral axon process, central axon process, soma, sensory ganglia. NEU 3. Write the Nernst equation, and explain the effects of altering the intracellular or extracellular Na+, K+, Cl-, or Ca2+concentration on the equilibrium potential for that ion. NEU 4. Describe the normal distribution of Na+, K+, and Cl-across the cell membrane, and using the chord conductance (Goldman) equation, explain how the relative permeabilities of these ions create a resting membrane potential. NEU 5. Describe ionic basis of an action potential. NEU 6. Distinguish the effects of hyperkalemia, hypercalcemia, and hypoxia on the resting membrane and action potential. NEU 7. Explain how the abnormal function of ion channels (channelopathies) can alter the resting membrane and action potential. 1 NEU 8. Describe the ionic basis of each of the following local graded potentials: excitatory post synaptic potential (EPSP), inhibitory post synaptic potential (IPSP), end plate potential (EPP) and a receptor (generator) potential. NEU 9. Contrast the generation and conduction of graded potentials (EPSP and IPSP) with those of action potentials. NEU 10. On a diagram of a motor neuron, indicate where you would most likely find IPSP, EPSP, action potential trigger point, and release of neurotransmitter. NEU 11. On a diagram of a sensory neuron, indicate where you would most likely find receptor potential or generator potential, action potential trigger point, and release of neurotransmitter. NEU 12. Describe how focal depolarization (EPSP) or hyperpolarization (IPSP) of a neuron can initiate action potential initiation by the processes of temporal and spatial summation. NEU 13. Describe the functional role of myelin in promoting saltatory conduction, contrasting the differences between the CNS and PNS. NEU 14. Describe the basis for the calculation of the space constant and time constant of neuron process. NEU 15. Define membrane capacitance and identify how membrane capacitance affects the spread of current in myelinated and unmyelinated neurons. NEU 16. Describe the effects of demyelination on action potential propagation and nerve conduction and the outcomes for recovery in CNS vs. PNS. NEU 17. Compare conduction velocities in a compound nerve, identifying how the diameter and myelination lead to differences in conduction velocity. NEU 18. Describe how inhibitory and excitatory post-synaptic potentials can alter synaptic transmission. Neurochemistry NEU 21. Compare electrical and chemical synapses based on velocity of transmission, fidelity, and the possibility for neuromodulation (facilitation or inhibition). NEU 22. Describe chemical neurotransmission, listing in correct temporal sequence events beginning with the arrival of a wave of depolarization at the pre-synaptic membrane and ending with a graded potential generated at the post-synaptic membrane. NEU 23. Define the characteristics of a classical neurotransmitter. Excitable Cells CE 24. Define the following properties of ion channels: gating, activation, and inactivation. CE 25. State the cell properties that determine the rate of electronic conduction. CE 26. Differentiate between the properties of electrotonic conduction, conduction of an action potential, and saltatory conduction. Identify regions of a neuron where each type of electrical activity may be found. CE 27. Contrast the cell to cell spread of depolarization at a chemical synapse with that at a gap 2 junction based on speed and fidelity (success rate). At the chemical synapse, contrast the terms temporal summation and spatial summation. CE 28. Understand the principle of the voltage clamp and how it is used to identify the ionic selectivity of channels. CE 29. Contrast the gating of ion-selective channels by extracellular ligands, intracellular ligands, stretch, and voltage. CE 30. Know the properties of voltage-gated Na+, K+, and Ca2+channels, and understand that voltage influences their gating, activation, and inactivation. CE 31. Understand how the activity of voltage-gated Na+, K+, and Ca2+ channels generates an action potential and the roles of those channels in each phase (depolarization, overshoot, repolarization, hyperpolarization) of the action potential. CE 32. Contrast the mechanisms by which an action potential is propagated along both nonmyelinated and myelinated axons. Predict the consequence on action potential propagation in the early and late stages of demyelinating diseases, such as multiple sclerosis. General Principles for Skeletal Muscle MU 1. Explain the overall transmembrane signaling steps whereby increases in cytosolic calcium initiate crossbridge cycling. MU 2. Identify the multiple sources, localization, and roles of calcium in muscle contraction and relaxation. MU 3. Draw a myosin molecule and label the subunits (heavy chains, light chains) and describe the function of the subunits. MU 4. Diagram the structure of the thick and thin myofilaments and label the constituent proteins. MU 5. Diagram the chemical and mechanical steps in the cross-bridge cycle, and explain how the cross-bridge cycle results in shortening of the muscle. MU 6. Explain the relationship of preload, afterload and total load in the time course of an isotonic contraction. MU 7. Distinguish between an isometric and isotonic contraction. MU 8. Draw the length versus force diagram for muscle and label the three lines that represent passive (resting), active, and total force. Describe the molecular origin of these forces. MU 9. Explain the interaction of the length:force and the force:velocity relationships and how they vary. MU 10. List the energy sources of muscle contraction and rank the sources with respect to their relative speed and capacity to supply ATP for contraction. MU 11. Draw and label a skeletal muscle at all anatomical levels, from the whole muscle to the molecular components of the sarcomere. At the sarcomere level, include at least two different stages of myofilament overlap. MU 12. Describe the relationship of the myosin-thick filament bare zone to the shape of the active length:force relationship. 3 Control of Skeletal Muscle Contraction: Excitation-Contraction Coupling and Neuromuscular Transmission MU 13. List the steps in excitation-contraction coupling in skeletal muscle, and describe the roles of the sarcolemma, transverse tubules, sarcoplasmic reticulum, thin filaments, and calcium ions. MU 14. Describe the roles of ATP in skeletal muscle contraction and relaxation. MU 15. Draw the structure of the neuromuscular junction. MU 16. List in sequence the steps involved in neuromuscular transmission in skeletal muscle and point out the location of each step on a diagram of the neuromuscular junction. MU 17. Distinguish between an endplate potential and an action potential in skeletal muscle. MU 18. List the possible sites for blocking neuromuscular transmission in skeletal muscle and provide an example of an agent that could cause blockage at each site. Mechanics and Energetics of Skeletal Muscle Contraction MU 19. Distinguish between a twitch and tetanus in skeletal muscle and explain why a twitch is smaller in amplitude than tetanus and the continuum of force development between a twitch and tetanus including the intracellular events. MU 20. Draw force versus velocity relationships for two skeletal muscles of equal maximum force generating capacity but of different maximum velocities of shortening. MU 21. Using a diagram, relate the power output of skeletal muscle to its force versus velocity relationship. MU 22. Describe the influence of skeletal muscle tendons on contractile function. MU 23. Define muscular fatigue. List some intracellular factors that can cause fatigue. MU 24. Construct a table of structural, enzymatic, and functional features of the three major categories (fast-glycolytic, fast-oxidative-glycolytic, and slow-oxidative fiber types) of skeletal muscle fiber types and their relative plasticity. MU 25. Describe the role of the myosin crossbridges acting in parallel to determine active force and the rate of crossbridge recycling to determine muscle speed of shortening and rate of ATP utilization during contraction. MU 26. Describe how the origin and insertion of a skeletal muscle to the skeleton can influence mechanical performance of the muscle. MU 27. Define a motor unit and describe the order of recruitment of motor units during skeletal muscle contraction of varying strengths. 4