Biology subjects

Zhang, D.-Q.

Publications and source records attributed to Zhang, D.-Q..

3 recordsLinked to original sources

bioRxiv2026

GABAergic TH2 Amacrine Cells Participate in Spontaneous Wave Activity in the Developing Retina

Amacrine cells (ACs) are retinal interneurons that regulate synaptic transmission from bipolar cells to retinal ganglion cells (RGCs) and play essential roles in object motion detection, contrast sensitivity, and light adaptation. A subtype of GABAergic ACs identified using a tyrosine hydroxylase (TH) promoter-driven green fluorescent protein (GFP) mouse line has been termed TH2 amacrine cells (TH2-ACs). Although TH2-ACs contribute to the feature selectivity of object-motion signals in the adult retina, their functional properties during early postnatal development remain unclear. Using genetic mouse models, electrophysiology, immunohistochemistry, and calcium imaging, we show that TH2-ACs exhibit spontaneous rhythmic depolarizations during development. In the first postnatal week, these depolarizations were abolished by acetylcholine receptor antagonists, indicating that TH2-ACs are excited by starburst amacrine cells (SACs) via spontaneous cholinergic retinal waves. During the second postnatal week, rhythmic depolarizations persisted but were blocked by glutamate receptor antagonists, demonstrating that TH2-ACs are subsequently driven by bipolar cells through glutamatergic waves. Calcium imaging further revealed that this activity propagates across the TH2-AC network in a wave-like manner, potentially resulting in spatially and temporally patterned GABA release. Pharmacological blockades of GABAA receptors significantly enhanced glutamatergic wave activity in SACs and RGCs, indicating that GABAergic signaling from TH2-ACs participates in exerting inhibitory control over retinal waves. Together, these findings identify TH2-ACs as active participants in the development of retinal wave circuits and suggest that this participation via GABA signaling could contribute to activity-dependent refinement of retinal circuits underlying object motion processing. Key pointsO_LITH2 amacrine cells are excited by starburst amacrine cells through cholinergic retinal wave activity during the first postnatal week. C_LIO_LIDuring the second postnatal week, TH2 amacrine cells are driven by bipolar cells via glutamatergic retinal wave activity. C_LIO_LIThe dense dendritic arborization of TH2 amacrine cells enables their participation in the propagation of both cholinergic and glutamatergic waves. C_LIO_LIWave-like GABA release from TH2 amacrine cells contributes to the modulation of retinal wave activity through activation of GABAA receptors. C_LI

neuroscience↗

bioRxiv2024

Dopaminergic amacrine cells express HCN channels in the developing and adult mouse retina

PurposeTo determine the molecular and functional expression of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in developing and mature dopaminergic amacrine cells (DACs), the sole source of ocular dopamine that plays a vital role in visual function and eye development. MethodsHCN channels are encoded by isoforms 1-4. HCN1, HCN2, and HCN4 were immunostained in retinal slices obtained from mice at postnatal day 4 (P4), P8, and P12 as well as in adults. Each HCN channel isoform was also immunostained with tyrosine hydroxylase, a marker for DACs, at P12 and adult retinas. Genetically-marked DACs were recorded in flat-mount retina preparation using a whole-cell current-clamp technique. ResultsHCN1 was expressed in rods/cones, amacrine cells, and retinal ganglion cells (RGCs) at P4, along with bipolar cells by P12. Different from HCN1, HCN2 and HCN4 were each expressed in amacrine cells and RGCs at P4, along with bipolar cells by P8, and in rods/cones by P12. Double immunostaining shows that each of the three isoforms was expressed in approximately half of DACs at P12 but in almost all DACs in adults. Electrophysiology results demonstrate that HCN channel isoforms form functional HCN channels, and the pharmacological blockade of HCN channels reduced the spontaneous firing frequency in most DACs. ConclusionsEach class of retinal neurons may use different isoforms of HCN channels to function during development. HCN1, HCN2, and HCN4 form functional HCN channels in DACs, which appears to modulate their spontaneous firing activity.

neuroscience↗

bioRxiv2020

Spontaneous depolarization-induced action potentials of ON-starburst amacrine cells during cholinergic and glutamatergic retinal waves

Correlated spontaneous activity in the developing retina (termed "retinal waves") plays an instructive role in refining neural circuits of the visual system. Depolarizing (ON) and hyperpolarizing (OFF) starburst amacrine cells (SACs) initiate and propagate cholinergic retinal waves. Where cholinergic retinal waves stop, SACs are thought to be driven by glutamatergic retinal waves initiated by ON-bipolar cells. However, the properties and function of cholinergic and glutamatergic waves in ON- and OFF-SACs still remain poorly understood. As expected, we found that both SAC subtypes exhibited spontaneous rhythmic depolarization during cholinergic and glutamatergic waves. Interestingly, ON-SACs had wave-induced action potentials (APs) in an age-dependent manner, but OFF-SACs did not. We further found that the number of APs in ON-SACs was correlated with the amplitude of Ca2+ transients of either ON- or OFF-SACs during cholinergic retinal waves. These results advance the understanding of the cellular mechanisms underlying correlated spontaneous activity in the developing retina.

neuroscience↗