Abstract
Purpose: :
The mouse retina represents an ideal model to study alterations in the physiological activity after the loss of one cell class, the photoreceptors. It has been reported that spontaneous ganglion cell activity increases and becomes rhythmic in rod degenerated (rd1) mouse retinas. The mechanisms leading to this aberrant behaviour are still unknown. Here we assess the contribution of electrical coupling between retinal ganglion cells in rd1 retinas.
Methods: :
Extracellular action potentials were recorded simultaneously from up to 100 retinal ganglion cells (RGC) in the in vitro retina of rd1 and wild type (wt) mouse using a multi-transistor array (1mm2) with 16384 sensor sites. Spontaneous spiking activity in adult retinas was identified using a sorting algorithm based on the high spatial resolution of the sensors. Cross-correlation functions (CCFs) upon spontaneous spikes were calculated for cell pairs. Pharmacological blockade of excitatory glutamatergic input or electrical synaptic transmission was performed by using (100µM DNQX, 20µM AP7) or meclofenamic acid (100 µM) respectively.
Results: :
In the adult rd1 retina extensive electrical coupling among RGCs was identified based on reciprocal narrow cross-correlations. This correlation type persisted in the presence of glutamatergic receptor blockers. The coupling strength in the two conditions was not altered. Individual rd1 RGCs were electrically coupled with up to four nearby cells. Furthermore, the electrical coupling strength among rd1 RGCs was twice as strong as the strength calculated among wt RGCs. In rd1 retinas up to 50% of the identified cells were functionally connected, whereas in each wt retinas only few coupled cells were identified.In both retinal types (rd1 and wt) electrical coupling was found only among cells separated by less than 220 µm.
Conclusions: :
Functional electrical coupling was identified among rd1 and wt RGCs. The strong and extensive electrical connectivity in rd1 retinas is partially responsible for the hyperactivity of rd1 RGCs.
Keywords: retinal degenerations: cell biology • gap junctions/coupling • ganglion cells