Sarah and Gabby’s paper is accepted into Neural Development

Nuclei-specific differences in nerve terminal distribution, morphology, and development in mouse visual thalamus

Sarah Hammer1,2*, Gabriela Carrillo 1,3*, Gubbi Govindaiah6*, Aboozar Monavarfeshani 1,4, Joseph S. Bircher 1,5, Jianmin Su1, William Guido6, Michael A. Fox1,4,5§

Mouse visual thalamus has emerged as a powerful model for understanding the mechanisms underlying neural circuit formation and function. Three distinct nuclei within mouse thalamus receive retinal input, the dorsal lateral geniculate nucleus (dLGN), the ventral lateral geniculate nucleus (vLGN), and the intergeniculate nucleus (IGL). However, in each of these nuclei retinal inputs are vastly outnumbered by non-retinal inputs that arise from cortical and subcortical sources. Although retinal and non-retinal terminals associated within dLGN circuitry have been well characterized, we know little about nerve terminal organization, distribution and development in other nuclei of mouse visual thalamus. Immunolabeling specific subsets of synapses with antibodies against vesicle-associated neurotransmitter transporters or neurotransmitter synthesizing enzymes revealed significant differences in the composition, distribution and morphology of non-retinal terminals in dLGN, vLGN and IGL. For example, inhibitory terminals are more densely packed in vLGN and cortical terminals are more densely distributed in dLGN. Overall, synaptic terminal density appears least dense in IGL. Similar nuclei-specific differences were observed for retinal terminals using immunolabeling, genetic labeling, axonal tracing and serial block face scanning electron microscopy: retinal terminals are smaller, less morphologically complex, and more densely distributed in vLGN than in dLGN. Since glutamatergic terminal size often correlates with synaptic function, we used in vitro whole cell recordings and optic tract stimulation in acutely prepared thalamic slices to reveal that excitatory postsynaptic currents (EPSCs) are considerably smaller in vLGN and show distinct responses following paired stimuli. Finally, anterograde labeling of retinal terminals throughout early postnatal development revealed that anatomical differences in retinal nerve terminal structure are not observable as synapses initially formed, but rather developed as retinogeniculate circuits mature.