The Ribbon Synapse and the dAMPA glutamate receptor

We are faced with a paradox in that the dAMPA receptor is rapidly desensitizing yet we are confident that this receptor underlies the stimulation of the sustained-on ganglion cell in the retina. In this exercise we will compare the response of a dAMPA receptor to a constant pulse of glutamate as seen in whole cell recordings in the laboratory and in a simulation of a ribbon synapse.

The ribbon synapse is modeled as having 20 release sites. Each release site is independent of the other. Glutamate is released as a brief alpha-function pulse with a peak at 1.5 ms. The rate of release can be controlled but release is stochastic. If you set a release rate of 5 per sec., on the average, 5 vesicles will be released every second; but the number of releases in a given one-second interval may vary from this.

Our model consists of a single compartment that has a dAMPA kinetic scheme derived from Partin, etal. for the rat cerebellar cortex. We will look at the voltage response of the conductance change elicited by the two glutamate stimulus conditions. Both stimulus schemes begin 10ms. after the start of the simulation and terminate 500ms. later. The maximum concentration of glutamate in both cases is 1mM.

Bring up the simulation by typing:                              spike ribbon.hoc -

The top graph window records the voltage over time within the single compartment. The second shows the glutamate concentration in mM released from one of the ribbon release sites; the third window pulse application glutamate concentration.

The top panel sets the maximum conductance of both ribbon and pulse glutamate application as well as the rate of ribbon release. The ‘Insert Box’ indicates the insertion of passive and active (5-channel) mechanisms and a calcium pump.

Experiment 1 - Passive mechanism only

-Check OFF (remove) ‘cad’ and ‘spike’ in the Insert box.

-Set ‘Pulse Gmax’ = 0.0013 Siemens; ‘Ribbon Gmax’ = 0

-‘Keep Lines’ in the voltage window (select with right mouse button’)

-Press ‘Init & Run’

-Repeat above setting ‘Ribbon Gmax’ = 0.0013 and ‘Pulse Gmax’ = 0

                        Observe the difference between the two conditions.

Experiment 2 - Active and passive mechanisms

-Check ON ‘cad’ and ‘spike’ in the Insert box.

-‘Erase’ selecting with the right mouse button.

-Repeat the conditions as in Experiment 1.

                        Observe

Try altering the ribbon release rate from 1 to 25. What is the most effective rate?

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