May 2008
Volume 49, Issue 13
ARVO Annual Meeting Abstract  |   May 2008
Serial Inhibition Spatially Tunes Presynaptic Inhibition in Retinal Bipolar Cells
Author Affiliations & Notes
  • E. D. Eggers
    Ophthalmology & Visual Sciences, Washington Univ Sch of Medicine, Saint Louis, Missouri
  • P. D. Lukasiewicz
    Ophthalmology & Visual Sciences, Washington Univ Sch of Medicine, Saint Louis, Missouri
  • Footnotes
    Commercial Relationships  E.D. Eggers, None; P.D. Lukasiewicz, None.
  • Footnotes
    Support  NIH grants F32 EY15629 (EDE); EY08922 (PDL); EY02687 (W.U. Dept. Ophthalmology), Research to Prevent Blindness, McDonnell Center for Higher Brain Function and The M. Bauer Foundation
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 5808. doi:
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    • Get Citation

      E. D. Eggers, P. D. Lukasiewicz; Serial Inhibition Spatially Tunes Presynaptic Inhibition in Retinal Bipolar Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5808.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Spatial tuning of bipolar cell (BC) presynaptic inhibition is important because it contributes to ganglion cell receptive field surrounds. Although the inhibitory surround is thought to increase with increasing light size, up to some maximum value, our previous findings suggest that serial inhibitory connections between amacrine cells limit the extent of BC inhibition. Blocking serial inhibitory connections with GABAAR antagonists significantly increased light-evoked inhibitory postsynaptic currents (L-IPSCs) evoked by large 825 µm stimuli, suggesting that L-IPSCs are normally inhibited by serial connections. However, similar blockade of GABAARs decreased L-IPSCs evoked by small 25 µm stimuli by decreasing direct GABAAR-mediated input, suggesting that the impact of serial connections is spatially regulated. Here, we investigated whether serial connections spatially tuned BC L-IPSCs.

Methods: : L-IPSCs were recorded from BCs in dark-adapted mouse retinal slices in the whole-cell voltage clamp mode at the cation reversal potential. Light stimuli were generated by a DLP, projected through the microscope objective and centered on the recorded BC. A suppression index (SI) that represents the suppression of L-IPSCs to large light stimuli was calculated from the area response function (ARF) - the charge transfer of the response to different stimulus sizes. The SI is the maximum response divided by the response to the largest light stimulus (825 µm); an index of 1 indicates no suppression.

Results: : To determine the spatial extent of BC inhibition, we measured the ARF of BC L-IPSCs. For all BC types, L-IPSCs increased and then decreased with increasing stimulus size. The SI values were significantly greater than 1 for all BC types, indicating suppression of the L-IPSC with large stimuli. Blocking serial connections between amacrine cells with the GABAAR antagonist bicuculline changed the ARFs. In the presence of bicuculline, the L-IPSCs increased with increasing light size. In contrast to control conditions, the SI values were not different from 1, indicating no suppression of the L-IPSC by large stimuli after serial inhibition was eliminated.

Conclusions: : We found that the spatial extent of BC L-IPSCs was modulated by GABAAR-mediated serial inhibitory connections. For all BC types, the ARF maximum response was not elicited by the largest stimuli (825 µm), but rather by intermediate light stimuli (~ 400 µm). As presynaptic inhibition of BCs is important for determining center-surround organization of ganglion cell responses, this spatial tuning of inhibition may create additional surround components.

Keywords: inhibitory neurotransmitters • retinal connections, networks, circuitry • retina: proximal (bipolar, amacrine, and ganglion cells) 

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