Name: Hours:_ BIOLOGY 640

CELLULAR NEUROSCIENCE
PROBLEM SET #4 (45 points total)

Coworkers:

READ CAREFULLY!! This problem set is intended to help you determine your level of understanding of the material presented so far. You may use any resource in doing the assignment, and you may discuss this work with others. However, you may not look at another person's written answers and you must use your own words in your written answers. You must name all coworkers on the front page of your answers, and you must cite all sources. To help us assess the difficulty of this assignment, please also indicate the number of hours you spent working to complete the problem set. Problem Set #4 is due Tuesday, May 1st, by Midnight. To get full credit for your answers consider the following: Conceptual problems: Write in complete, clear sentences. Most questions can be answered succinctly. Avoid vague answers and excess verbiage. Avoid long, rambling paragraphs. In some cases outlining an answer or presenting it in table form maximizes clarity. Equations: Explain assumptions and how you determined which equation to use; show all important steps; include units, e.g. mm, moles/liter, etc. in your answer. Experimental designs: make sure to include concrete ways to measure your expected results. For example, dont just write after administering drug X, I check whether the cell membrane is thinner, but also describe how exactly you would test whether the membrane is thinner or not. Refer to the online reader for examples as to how to answer these questions correctly. I. Evidence for Presynaptic Nature of LTP: (15 points)

In class we discussed the evidence supporting that induction and expression of LTP were postsynaptic. While this is the leading theory these days, for a long time there was a big debate of whether LTP was pre or postsynaptic. Below is a histogram of PSP size for a CA1 synapse before (Control) and after (After-LTP) the induction of LTP using a 100Hz protocol. These recordings are from a synapse in the CNS, so there was no need to change Ca2+ concentrations because postsynaptic responses were small enough to evaluate this way.

A. How do these results support a presynaptic mechanism for LTP? Explain in detail. B. From our notes and the textbook: What is the evidence that the induction of LTP is postsynaptic? II. Glial Cells: (15 points)

Glial cells are the most abundant cells in the nervous system. They share many properties with neurons. When studying glial cells, one of the things that surprised researchers was that the resting potential of glial cells was much more negative than that of neurons. Below is a figure that shows measurements of glial cell membrane potentials as the concentration of extracellular K was changed.

A. Make a table comparing Glial cells and neurons in at least 8 points of comparison. B. Estimate the equilibrium potential of K+ for this cell. C. Explain why it that the resting potential of glial cells is so negative. III. NMDA Receptors and Plasticity: (15 points)

The direction of activity-dependent long term changes in synaptic strength (i.e. LTP vs. LTD) is thought to be determined by the level and the timing of Ca2+ influx into postsynaptic spines when the NMDA receptor is activated.

Receptors containing 2 NR1 subunits and 2 NR2A subunits (NR1/2A) show the activation and deactivation kinetics shown in the figure to the right. Receptors containing 2 NR1 subunits and 2 NR2B subunits (NR1/2B) show different activation and deactivation kinetics. These are shown on the left too. EC50 is the effective concentration for activating 50% of the receptors.

NR1/2A receptors have an EC50 value for glutamate of 4.8 M. NR1/2B receptors have an EC50 value for glutamate of 1.8 M. Consider the following hypothetical situation: Equal numbers of NR1/2A receptors and NR1/2B receptors are randomly distributed in the postsynaptic membrane of synapses in a brain area. Recordings from the synapses in this brain area display frequencydependent synaptic plasticity as described by Graph 1. A stimulus at a frequency < 5 Hz produces LTD. A stimulus at a frequency > 5 Hz produces LTP. A 5 Hz tetanic stimulus produces no change in synaptic strength. Therefore, 5 Hz is referred to as the cross-over frequency for this synapse.

Graph 1. The ordinate represents synaptic strength, and the abscissa represents frequency of a brief tetanic stimulation. A. If all of the NR1/2A receptors were changed to NR1/2B receptors, what change would you expect in the crossover frequency for the synapse? Explain. B. If, instead, all of the NR1/2B receptors were changed to NR1/2A receptors, now what change would you expect in the crossover frequency for the synapse? Explain.