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Microsoft Word - FH_Homework_3_BMS325_SP20.docx 1 BMS 325 Name_____________________________ Spring 2020 Homework 3 Student ID_________________________ Print this document and mark your answers here. Print 2-sided or staple pages together before turning in and put your name on both pages. Due in class on Wednesday, February 19 The series of questions and exercises in this homework 3 are designed to show you how electrical information travels from a synapse in a dendrite to the axon initial segment. Along the way you should learn how membrane resistance and neuron shape modify transmission, spatial and temporal summation. MetaNeuron Simulator Exercises 1- Go to the webpage http://www.metaneuron.org/ & download the MetaNeuron Program. 2- Chose your lesson in tool bar under “lesson”. 3- Under “file”, click “Restore lesson to defaults”. Use this every time you see “restore defaults” below. 4- Remember that you can measure peaks of current and Vm on the graphs by clicking on them. Please give a short answer to the following questions (2-3 sentences). Effect of dendritic morphology on single Synaptic potentials Synapses are mostly at dendrites and dendrites are not myelinated. This means that injection of current at synapses propagate in the synapse via passive current. Since dendrites are not myelinated current inside the cell leaks out and spread internally. Therefore, both membrane resistance and internal resistance play a key role in how synaptic potentials are spread in dendrites and eventually get to the axon initial- segment. The aim of this exercise is for you to get a feel of how both these parameters play a key role in the propagation of EPSPs and how dendrite diameter now plays a role in this spread. Chose Lesson 3. Restore Lesson default. Change the Stimulus to Synaptic potential. Set the amplitude to 20 µA. In the Dendrite/Axon Properties box, set the membrane resistance to 50kΩ.cm2. Then click on the white button, which should now indicate RANGE. In the Range box below set the end value to 50 and increment 5. 1) How does the increase in membrane resistance change the decay of the synaptic potential? 2 Restore Lesson default. Change the Stimulus to Synaptic potential. Set the amplitude to 20 µA. In the Dendrite/Axon Properties box, set the internal resistance to 10Ω.cm. Then click on the white button, which should now indicate RANGE. In the Range box below set the end value to 250 and increment 50. 2) How does the increase in internal resistance change the decay of the synaptic potential? Restore Lesson default. Change the Stimulus to Synaptic potential. Set the amplitude to 20 µA. In the Dendrite/Axon Properties box Set the diameter to 1 instead of 0.1. Then click on the white button, which should now indicate RANGE. In the Range box below set the end value to 10. 3) Why do you think changing the size of the axon/dendrite changes the spread of synaptic potential? Effect of dendritic morphology on spatial and temporal summation Neurons tightly control the size of dendrites, their shape and membrane composition, regulating the membrane resistance, the internal resistance and way synaptic potential propagate. This has profound effects on temporal and spatial summation of synaptic potentials. Chose Lesson 2. Restore lesson to default. Change the Stimulus to Synaptic potential. Pick Set the amplitude to 20 µA. In stimulus Train box, set the number of stimuli to 5. Set the membrane resistance box to 1, then 10, then 20, the click the box to change it to RANGE. 4) Explain why changing the membrane resistance changes the temporal summation. What do you think this means for 2 stimuli arriving at a thin spine or large dendrite? 3 Synaptic Potential and current: In this lesson we are modeling how a synapse in a neuron would react to either excitatory or inhibitory stimulation. The aim is to understand that ion flows at synapses are also determined by Vm and Eion, which can lead to either depolarization or hyperpolarization depending on Vm and Eion. We will simulate synaptic excitation (or EPSP) by using a channel permeable to Na+/K+ mimicking glutamate-gated ion channels and synaptic inhibition (or IPSP) using a channel permeable to Cl-. The relative permeabilities of Na+/K+ determine the reversal potential for the synapse. The equilibrium potentials for Na+, K+ and Cl- in the model are +50, -77 and -75mV, respectively. The reversal potential of the synapse can be determined by varying the membrane potential of the neuron (Yellow trace) and noting the potential at which the synaptic response reverses polarity. The membrane potential is varied by adjusting the “holding current”. The currents flowing through the receptor channel are shown to the right: Na+ (green) and K+ (blue), for the excitatory receptor and Cl- (orange) for the “inhibitory” receptor. Chose Lesson 6: Starting with the default parameter values, note that a depolarizing response (yellow trace) is generated. This represents an excitatory postsynaptic potential (EPSP) generated by the opening of a ligand gated ion channel. Using the default values, the receptor has an Na+: K+ permeability ratio of 1.2 :1. This is a good approximation of an AMPA-type glutamate receptor. The depolarization is generated by a large Na+ influx (green trace), which is partially offset by a smaller K+ efflux (blue trace). Sometimes when a neuron receives a synaptic stimulus it is already depolarized by another event. We will simulate how depolarizing the postsynaptic cell modifies the effect of the incoming stimulus. In the Holding Current box, chose 0, 50, 100, 110, 120 µA. Note what is happening to the stimulus and the direction of Na+ and K+ flow Now select the fast-inhibitory synapse. Vary the Holding current again -50, -20, 0, 25, 50, 100 µA. Note what is happening to the stimulus and the direction of Cl- current. 5) Explain why changing the postsynaptic membrane potential or Vm as we had it before, changes the effect of the synaptic stimulus. As before with axons, the ions want to make Vm=Eion. An EPSP is not an Action Potential, it is just a depolarization of the membrane due to ligand gated channels or injection of current