Thalamic activity regulates interneuron density in the developing visual thalamus

Neural activity is a fundamental driver of early circuit assembly, yet how it shapes the distribution of inhibitory neurons across sensory networks remains poorly understood. Establishing an appropriate balance between excitation and inhibition is essential for effective sensory processing, but the contribution of activity-dependent mechanisms to interneuron allocation across subcortical and cortical stations is unclear. Here, we use region-specific transgenic mouse models of either sex to selectively manipulate activity at distinct loci and developmental stages of the visual pathway. We show that intrinsic thalamic activity is a key regulator of interneuron density in the dorsolateral geniculate nucleus during early postnatal development. Disruption of thalamic activity leads to persistent increases in interneuron proportion, independent of retinal axon targeting. Moreover, altered thalamic activity propagates to the cortex, producing layer-specific changes in parvalbumin- and somatostatin-expressing interneuron populations in primary visual cortex. Together, our findings identify intrinsic thalamic activity as a central organizer of inhibitory circuit assembly across the visual system, coordinating interneuron integration in both thalamus and cortex during critical developmental windows. Significance Statement The proper integration of inhibitory interneurons into thalamic circuits is essential for establishing balanced excitatory–inhibitory activity in the visual system. Previous work has highlighted the role of retinal input in this process, but the contribution of intrinsic thalamic activity has remained unclear. Here, we show that thalamic activity is critical for determining interneuron density in the dorsolateral geniculate nucleus. In contrast, removal of retinal input alters interneuron positioning but not overall density. These findings reveal that intrinsic thalamic activity and retinal input act through distinct yet complementary mechanisms to shape thalamic inhibitory circuits, with lasting consequences for cortical circuit maturation.