Abstract
Purpose: :
Neuronal coupling via gap junctions (gjs) is believed to underlie concerted activity amongst ganglion cells (GCs) in the retina. In addition, many GCs are also coupled to neighboring amacrine cells (ACs). Here we studied the concerted activity between coupled ACs and GCs in the rabbit and mouse retinas.
Methods: :
We targeted GCs in the albino rabbit and td Tomato mouse retinas, which, based on Neurobiotin and Po-Pro-1 labeling, were tracer coupled to neighboring displaced ACs in the GCL. We then performed dual extracellular recordings from coupled GC/AC pairs and computed their concerted spontaneous spike activity with cross-correlogram functions (CCFs). Chemical synaptic transmission was blocked with a cocktail of MK-801, CNQX, PTX, strychnine, and L-AP4. Gjs were blocked with 18-beta-glycyrrhetinic acid (GA) or meclofenamic acid (MFA).
Results: :
In the rabbit, we targeted a GC subtype with an elongated, ovoid soma 18-20 µm in diameter. We injected these GCs with Po-Pro-1 and Neurobiotin and found that they were extensively coupled to neighboring displaced ACs. Simultaneous recordings were made from coupled GCs and ACs, both of which showed robust spike activity. The concerted spontaneous activity was reflected by two main components in the CCFs. These consisted of a single sharp peak at time zero indicative of synchronous activity, which was flanked by two symmetrical shoulders with latencies of 6-10 msec from time zero. Application of a cocktail to block chemical synaptic transmission resulted in a significant reduction in the peak component, but had only a minor effect on the shoulder components. In contrast, application of the gj blockers GA or MFA significantly reduced the shoulder components, but had little effect on the central peak. The CCFs for coupled AC/GC pairs in the mouse retina showed profiles similar to those seen in the rabbit. However, often the central peak was flanked by only a single shoulder. Pharmacological effects were similar to those seen in the rabbit.
Conclusions: :
Our results indicate that coupled ACs and GCs show both synchronous (peak) and short-latency (shoulder) concerted activity. Our drug studies indicate that the synchronous activity is likely generated by common excitatory chemical synaptic inputs, whereas the short-latency correlated firing is generated by electrical synaptic transmission via gjs. Interestingly, our results indicate that AC activity can generate spikes in coupled GCs, but also that GCs can drive activity of ACs. These data thus suggest a pathway for GC modulation of intraretinal signaling.
Keywords: gap junctions/coupling • ganglion cells • amacrine cells