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The Temporal and Spatial Characteristics of Amacrine-to-Amacrine Inhibition: Mapping Amacrine Cell Circuitry With Electrophysiology, Pharmacology, Morphology and Immunocytochemistry

  • Author(s): Hsueh, Hain-Ann
  • Advisor(s): Werblin, Frank S
  • et al.
Abstract

We studied the interactions between excitation and inhibition in morphologically-identified amacrine cells in the light-adapted rabbit retinal slice and wholemount using the patch clamp technique with pharmacology.

We found that the majority of ON amacrine cells received glycinergic OFF inhibition. About half of the OFF amacrine cells receive glycinergic ON inhibition. By mapping the receptive field of inhibition, we found that this glycinergic inhibition was typically smaller than the receptive field of excitation. In retinal slice, a minority of ON, OFF, ON-OFF amacrine cells received both glycinergic ON and GABAergic OFF inhibition. In retinal wholemount, ON-OFF inhibition was found to be glyceringic. These interactions were found in cells with diverse morphologies (wide and narrow cells, with either monostratified or diffuse processes). Most ON-OFF amacrine cells received no inhibition and had monostratified processes confined to the middle of the inner plexiform layer. Glycinergic inhibition was the dominant type of inhibition we measured in amacrine cells. The most common interaction between amacrine cells that we measured is "crossover inhibition," where OFF inhibits ON, and ON inhibits OFF.

After we recorded from amacrine cells, we identified their neurotransmitter content using immunocytochemical techniques, and correlated this with their morphological and physiological characteristics. We found that narrow cells, or cells that conveyed local information, usually contained glycine. Wide cells, or cells that conveyed global information, usually contained GABA. Some narrow field cells that received wide-field inhibition contained GABA. Some cells had receptive fields smaller than their dendritic fields, and appeared to be able to generate action potentials.

Data from electrophysiology, pharmacology, morphology and immunocytochemistry revealed that amacrine cells interact with one another using primarily glycine. GABAergic amacrine cells play a larger role in feedback and feedfoward inhibition to bipolar and ganglion cells than in amacrine cells. Narrow-field, glycinergic amacrine cells are primarily involved in crossover inhibition, which is also a common circuit topology in electronics. These interactions between amacrine cells forms the basis for the diverse inhibitory inputs to ganglion cells. With a deeper understanding of retinal circuits, we hope to design more effective retinal prostheses for the treatment of retinal disease.

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