The Influences Of Gabaergic Pathways On Concerted Activities In Chicken Retinal Ganglion Cells

In the present study, the firing activity of newly-hatched chicken retinal ganglion cells, the output neurons of retina, in response to specific light stimulation was investigated by using multi-electrode recording system. The main goal of this thesis is to study the different patterns of concerted activity among retinal ganglion cells and the influence of the main inhibitory pathway—the GABAergic pathway on the concerted activity.According to the peak width in the cross-correlation function, concerted activity can be classified into two different patterns. Ganglion cells of sustained subtype fired in precise synchrony with their adjacent neurons of the same subtype (peak width within 2 ms, termed synchronization). On the other hand, the activities of neighboring ganglion cells of transient subtype were correlated with distributed time lags (peak width between 7-25 ms, termed correlation). Pharmacological studies demonstrated that the intensity of the correlated activities between transient cells could be strengthened when exogenousγ-aminobutyric acid (GABA) was applied, and attenuated when GABA receptors were blocked by picrotoxin (PTX). Meanwhile, the GABAergic modulation on the synchronized firings between sustained cells was not consistent. These results suggest that in the chicken retina, GABAergic pathway(s) are likely involved in the modulation of the correlations between ganglion cells.Then we further investigated the correlated firings of adjacent ganglion cells of transient subtype. Since PTX could block both GABAA and GABAC receptors, we further applied the specific antagonist and agonist of GABAA receptors, bicuculline (BIC) and muscimol (MUS) respectively, and the specific antagonist of GABAC receptors, (1,2,5,6-tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA) to study which kind of receptor is more important to the regulation of correlated activity. Application of BIC could also significantly down-regulate the correlation strength, while MUS could potentiate the correlated activities. But TPMPA had no significant effect on both firing rate and correlation of transient ganglion cells. This suggests that GABAA-receptor-mediated inhibitory pathway may play a crucial role on the regulation of correlated activity. The activation of GABAA receptor could enhance the correlated firings between nearby ganglion cells.Furthermore, we developed a new measurement based on sub-sequence distribution discrepancy (Measurement of sub-sequence distribution discrepancy, MSDD) to analyze the spatial pattern of multiple spike train at the same time. MSDD is an efficient method when it is applied to analyze the concerted activities of a population under a certain condition. The result in the present study show that when this new method was applied to compare the concerted activities between two different conditions, it could reflect the changes of concerted pattern, but it could not reflect how the strength of concerted activities changes among a neuronal population.In summary, in the chicken retina, concerted activities within an assembly of ganglion cells may be increased while the firing activity was reduced with the activation of GABAA receptors. GABAA-receptor- mediated input exerts more significant inhibitory effect on the uncorrelated firing activities; at the mean time, correlated signals are largely remained, so that the efficiency of information transmission can be improved.