Abstract
Purpose::
In light, retinal On bipolar cells are depolarized due to the inactivation of the mGluR6 signaling cascade, which ultimately leads to opening of a synaptic cation channel. Our previous studies have suggested that open channels are driven into a desensitized state, providing a mechanism for restoration of the dark membrane potential in the presence of continuous illumination. However, our previous experiments have focused on desensitization in response to opening of all available synaptic channels. In the present study, we examined whether channel desensitization occurs when only a fraction of the available channels are opened, as would likely occur during normal illumination.
Methods::
Retinal slices from larval tiger salamander were prepared and On bipolar cells were identified by morphology after filling with Alexa 488, and their characteristic response to mGluR6 ligands. Synaptic channels were held in the closed state by a saturating concentration of glutamate in the bath (1 mM), and response to brief puffs of the mGluR6 antagonist LY341495 were obtained. Subsequently, the bath concentration of glutamate was lowered to 300 µM and a second puff response was elicited.
Results::
We find evidence for at least two population of bipolar cell, which respond differentially to lowered agonist concentration. In one type, lowering agonist concentration opened, and subsequently desensitized a fraction of synaptic channels, and a second puff LY341495 opened the remainder of the cation channel pool. The axons of these cells terminate deep in the inner plexiform layer. By contrast, in the other population of On cells, a decrease in ambient glutamate concentration profoundly depressed the response to a second puff of LY341495. The depression was far greater than predicted based on the model that only the fraction of channels opened by lowering glutamate are driven into the desensitized state.
Conclusions::
Based on both the cell morphology and physiology, our results suggest the presence of two types of On bipolar cells. One type, analogous to the sustained On bipolar reported previously by Awatramani and Slaughter (2000), displays a slower, less pronounced form of depression, while the other, analogous to transient On bipolar, possesses an additional mechanism to rapidly terminate signaling, and displays a robust form of synaptic depression.
Keywords: bipolar cells • retinal connections, networks, circuitry • electrophysiology: non-clinical