Abstract
Purpose :
Calcium-permeable AMPA receptors (CP-AMPARs) have been implicated in synaptic transmission and activity-dependent synaptic plasticity in ON (but not OFF) mouse retinal ganglion cells (GCs) (Xia et al., 2006, 2007; Jones et al., 2012). We tested whether there were differences in the functional expression of CP-AMPARs between the ON and OFF pathways of the primate retina.
Methods :
We made extracellular and whole-cell recordings from midget and parasol GCs in macaque retinal wholemounts under photopic background intensities. The light stimulus was a square-wave modulated spot (1Hz, 80% contrast) centered on the receptive field. To determine the contribution of CP-AMPARs to spiking or synaptic currents, we measured responses in the presence or absence of the CP-AMPAR blocker (IEM1460 (IEM), 50μM). In some experiments, 50μM D-AP5 was included to block NMDA receptors.
Results :
IEM blocked a sustained component of the stimulus-evoked response of ON midget GCs. Spiking was reduced from 45±12Hz in control to 13±15Hz in IEM (72±28% reduction, p=0.002, n=6). IEM suppressed the initial transient peak spike responses of ON midget GCs by 34±16% (control 99±38Hz; IEM 65±26Hz; p=0.014), and ON parasol GCs by 46±33% (control 95±23Hz; IEM 50±25Hz; p=0.013, n=6). IEM did not affect the sustained (control 33±15Hz; IEM 34±15Hz; p=0.941, n=5) or transient peak spike responses of OFF midget GCs (control 57±21Hz; IEM 72±16Hz; p=0.249). In ON midget GCs, the variance in the excitatory postsynaptic current (measured at -70mV) was unaffected by application of D-AP5 (σ=21.88±8.52pA vs σ=25.73±13.03pA), but was reduced with the addition of IEM (σ=8.90±5.11pA). Consistent with a baseline excitatory input mediated by CP-AMPARs, IEM strongly suppressed background spiking in ON midget by 98±3% (control 23±15Hz; IEM 0±0Hz; p=0.015) and in ON parasol GCs by 96±9% (control 8±4Hz; IEM 0±1Hz; p=0.003).
Conclusions :
Our results suggest that CP-AMPARs contribute to synaptic responses in the ON, but not the OFF pathway, of the primate retina. CP-AMPARs in ON midget and ON parasol GCs mediate sustained responses during light stimulation and under background illumination that may allow for more linear signal transmission in the ON pathway.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.