Abstract
Purpose: :
In several animal models of hereditary retinal degeneration, ganglion cells exhibit accelerated spontaneous activity that is driven in many cells by synaptic input 1,2. We report here that nonetheless a substantial proportion of retinal ganglion cells continue to discharge at rapid rates in the absence of synaptic transmission.
Methods: :
Extracellular action potentials were recorded simultaneously from 30-90 retinal ganglion cells in the in vitro retina of adult wild type (wt), rd1 or rd10 mice, using a multielectrode array. Spontaneous activity was monitored in control Ringer’s solution and in solution containing a mixture of DL-APB (100 υM), D-APV (100 υM), CNQX (20 υM), atropine (2 υM), hexamethonium bromide (100 υM), picrotoxin (20 υM), and strychnine (1 υM) in order to block synaptic transmission via mGluR6, NMDA, KA/QU, muscarinic and nicotinic acetylcholine, GABAA and GABAC, and glycinergic receptors, respectively.
Results: :
Blockade of the major excitatory and inhibitory neurotransmitter systems in the retina abolished or severely limited the ongoing spontaneous discharge in the majority of ganglion cells. However, this hyperactivity was only partially suppressed or continued unabated in up to 1/3 of all cells recorded in rd1 and rd10 retinas.
Conclusions: :
In two widely studied animal models of hereditary photoreceptor degeneration, the high frequency spontaneous activity that emerges in retinal ganglion cells is driven by a combination of synaptic and nonsynaptic mechanisms. The subpopulation of cells that sustains such hyperactivity in the absence of conventional synaptic transmission may serve as a "pacemaker" contributing to the heightened network activity seen under control conditions. Mechanisms underlying the excessive spontaneous firing of these cells may include nonsynaptic biochemical neurotransmission (e.g., dopaminergic), electrotonic communication through gap junctions, or intrinsic cellular properties altered by degenerative disease.
Keywords: retinal degenerations: cell biology • ganglion cells • neurotransmitters/neurotransmitter systems