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

ABSTRACT

Amacrine cells (ACs) are retinal interneurons that play essential roles in object motion detection, contrast sensitivity, and light adaptation. A subtype of GABAergic ACs identified in a tyrosine hydroxylase (TH) promoter‐driven green fluorescent protein (GFP) transgenic mouse line, termed TH2 amacrine cells (TH2 ACs), has recently been implicated in the feature selectivity of object‐motion signals in the adult retina. However, the functional properties and developmental roles of TH2 ACs remain largely unknown. Here, we demonstrate that TH2 ACs exhibit spontaneous rhythmic depolarizations during early postnatal retinal development. During the first postnatal week, these depolarizations are driven by cholinergic input from starburst amacrine cells (SACs). In the second postnatal week, spontaneous rhythmic activity persists but is mediated by glutamatergic input from bipolar cells. Calcium imaging further revealed that this spontaneous activity propagates across the TH2 AC network as retinal waves, potentially generating spatially and temporally patterned GABA release. Pharmacological experiments indicate that GABAergic signaling from TH2 ACs could contribute to the inhibitory regulation of the spatiotemporal properties of spontaneous retinal waves. Together, these findings identify TH2 ACs as active components of developing retinal wave circuits and suggest that they may contribute to the activity‐dependent refinement of retinal circuitry underlying object‐motion processing.