Thalamic Activity Regulates Interneuron Density in the Developing Visual Thalamus

Abstract

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.