Characterization of Retinal VIP-Amacrine Cell Development During the Critical Period

Retinal vasoactive intestinal peptide amacrine cells (VIP-ACs) play an important role in various retinal light-mediated pathological processes related to different developmental ocular diseases and even mental disorders. It is important to characterize the developmental changes in VIP-ACs to further elucidate their mechanisms of circuit function. We bred VIP-Cre mice with Ai14 and Ai32 to specifically label retinal VIP-ACs. The VIP-AC soma and spine density generally increased, from postnatal day (P)0 to P35, reaching adult levels at P14 and P28, respectively. The VIP-AC soma density curve was different with the VIP-AC spine density curve. The total retinal VIP content reached a high level plateau at P14 but was decreased in adults. From P14 to P16, the resting membrane potential (RMP) became more negative, and the input resistance decreased. Cell membrane capacitance (MC) showed three peaks at P7, P12 and P16. The RMP and MC reached a stable level similar to the adult level at P18, whereas input resistance reached a stable level at P21. The percentage of sustained voltage-dependent potassium currents peaked at P16 and remained stable thereafter. The spontaneous excitatory postsynaptic current and spontaneous inhibitory postsynaptic current frequencies and amplitudes, as well as charge transfer, peaked at P12 to P16; however, there were also secondary peaks at different time points. In conclusion, we found that the second, third and fourth weeks after birth were important periods of VIP-AC development. Many developmental changes occurred around eye opening. The development of soma, dendrite and electrophysiological properties showed uneven dynamics of progression. Cell differentiation may contribute to soma development whereas the changes of different ion channels may play important role for spine development.

Graphical Abstract

The second, third and fourth weeks after birth were important periods of VIP-AC development. VIP::Ai14 and VIP::Ai32 mice were used for soma and spine analysis, respectively. The developmental curves for VIP-AC soma have a distinct and longer platform, whereas the developmental curves for spine have a longer and smoother slopes. When the number of VIP-AC some is increasing, cell differentiation may play an important role. During the development of spine, the development of different ion channels is the most vital events. Kv-Ka represents the ion channels that conduct Ka, Kv-Kdr represents the ion channels that conduct Kdr, GABAR represents the inhibitory transmission and NMDAR represents the excitatory transmission. The events occur chronologically from left to right.