Dissociated Retinal Neurons Form Periodically Active Synaptic Circuits

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Abstract
Throughout the developing nervous system, immature circuits generate rhythmic activity patterns that influence the formation of adult networks. The cellular mechanisms underlying this spontaneous, correlated activity can be studied in dissociated neuronal cultures. Using calcium imaging and whole cell recording, we showed that cultured dissociated mammalian retinal neurons form networks that produce spontaneous, correlated, highly periodic activity. As the culture matures, the spatial correlations of the periodic calcium transients evolve from being highly synchronized across neighboring cells to propagating across the culture in a wavelike manner reminiscent of retinal waves recorded in vivo. Spontaneous calcium transients and synaptic currents were blocked either by cadmium, tetrodotoxin, or the glutamate receptor antagonist 6,7-dinitroquinoxaline, indicating that the periodic activity was driven primarily by synaptic transmission between retinal ganglion cells. Evoked responses between pairs of ganglion cells exhibited paired-pulse synaptic depression, and the time constant of recovery from this depression was similar to the interval between periodic events. These results suggest that synaptic depression may regulate the frequency of network activity. Together, these findings provide insight into how networks containing primarily excitatory connections generate highly correlated activity.