Abstract
Purpose:
Previous study from our laboratory showed that dopamine signaling, a classic feature of light-adaptation, is also required to increase the sensitivity of rod bipolar cells in darkness and at scotopic levels of background illumination. Knockout mice lacking the dopamine D1R receptor have smaller rod bipolar cell responses to light flashes under these conditions. Our data further indicated that D1R-dependent GABA release from other retinal neurons mediates this sensitization. The resulting chloride influx into rod bipolar cells via GABAcR receptor channels hyperpolarizes these cells in the resting state and allows them to produce larger depolarizing responses to light flashes. Because D1R activation is known to modulate the signaling of ionotropic glutamate receptors (iGluRs) in multiple neurons, we tested whether the effect of D1R knockout could be phenocopied by a pharmacological blockade of iGluR.
Methods:
We performed ERG recordings on dark-adapted wild type mice after intravitreal injection of the non-specific iGluR inhibitor cis-2,3-piperidinedicarboxylic acid (PDA). Responses to flashes of increasing intensity were recorded in the dark and in the presence of background light of various intensities. The b-wave sensitivities were determined by taking the ratio between the maximal response amplitude and the half-saturating flash intensity. All b-wave sensitivities were normalized to the dark-adapted b-wave sensitivity of control non-injected mice.
Results:
Intravitreal injection of PDA decreases the sensitivity of rod bipolar cells, both in the dark and in the presence of background light. The resulting relationship between response sensitivity and background light intensity replicated the corresponding relationship for the D1R knockout mice.
Conclusions:
Our data suggest that the enhancement of rod bipolar cell sensitivity by GABA may involve an interplay between D1R and iGluR signaling within the retinal neurons responsible for the underlying GABA release.
Keywords: 435 bipolar cells •
517 excitatory amino acid receptors •
502 dopamine