33 Hz for 30 min), neither TBS nor RFS further elevated the ampli

33 Hz for 30 min), neither TBS nor RFS further elevated the amplitude of e-EPSCs in RGCs (Figure 6C), indicating that RFS-induced synaptic enhancement occludes TBS-induced LTP. These results indicate that repeated visual inputs can induce LTP at BC-RGC synapses Dasatinib via mechanisms that may be shared by TBS-induced LTP. To further determine the physiological consequence of LTP at BC-RGC synapses, we investigated its effect on light-evoked responses in RGCs. In 3–6 dpf zebrafish larvae, whole-field flash (2 s duration) elicited both ON and OFF responses

in 61% of RGCs (259 of 425), and only ON (83 of 425) or OFF (83 of 425) responses in the rest of RGCs. Examples of light response subtypes are shown in Figure S8A. To assay light-evoked excitatory responses, we measured light-evoked EPSCs (l-EPSCs) in RGCs at the reversal potential of light-evoked inhibitory check details postsynaptic currents (ECl−; Figures S8B and S8C), with a low frequency of light stimulation (0.033 Hz). The magnitude of l-EPSCs in RGCs, as determined by the total integrated charge associated with l-EPSCs within a 100 ms window

after the onset of l-EPSCs (Du et al., 2009), remained stable for up to 50 min under control condition (Figure 7A). However, we observed persistent enhancement of light-evoked ON responses in eight out of eight ON-OFF and one out of one ON RGCs (157% ± 17% of the control, n = 9; p = 0.005; Figure 7B) after the induction of LTP at BC-RGC synapses by TBS applied at the INL. In addition, three out of eight ON-OFF RGCs

also showed a persistent increase in OFF responses after LTP induction. Thus, the LTP at BC-RGC synapses can substantially enhance light-evoked excitatory responses in RGCs, implicating its physiological relevance to retinal functions during development. To explore whether natural visual stimulation can potentiate visual responses of RGCs, we first examined the effect of RFS on light-evoked responses of RGCs in zebrafish larvae at 3–6 dpf. In nine out of ten RGCs possessing Histone demethylase ON responses, RFS induced persistent enhancement of light-evoked ON responses (167% ± 13% of the control, n = 10; p = 0.000007; Figure 8A), whereas five out of eight RGCs possessing OFF responses also showed a persistent increase in OFF responses after RFS. In addition, repetitive MBS (width, 6 μm; speed, 0.1 μm/ms; frequency, 0.25 Hz; duration, 5 min) also induced persistent enhancement of moving bar-evoked responses in five out of five RGCs examined (194% ± 24% of the control, n = 5; p = 0.004; Figure 8B). Furthermore, 30 min pre-exposure of repetitive moving bars occluded RFS-induced potentiation of flash-evoked responses of RGCs (91% ± 5% of the control, n = 5; p = 0.14; Figure 8C). Thus, different patterns of natural visual stimulation can enhance visual responses of RGCs, suggesting that visual experience is effective in modifying the function of developing retinal circuits.

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