Browsing by Author "Hammer, Sarah"
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- Multiple Retinal Axons Converge onto Relay Cells in the Adult Mouse ThalamusHammer, Sarah; Monavarfeshani, Aboozar; Lemon, Tyler; Su, Jianmin; Fox, Michael A. (Cell, 2015)Activity-dependent refinement of neural circuits is a fundamental principle of neural development. This process has been well studied at retinogeniculate synapses—synapses that form between retinal ganglion cells (RGCs) and relay cells within the dorsal lateral geniculate nucleus. Physiological studies suggest that shortly after birth, inputs from _20 RGCs converge onto relay cells. Subsequently, all but just one to two of these inputs are eliminated. Despite widespread acceptance, this notion is at odds with ultrastructural studies showing numerous retinal terminals clustering onto relay cell dendrites in the adult. Here, we explored this discrepancy using brainbow AAVs and serial block face scanning electron microscopy (SBFSEM). Results with both approaches demonstrate that terminals from numerous RGCs cluster onto relay cell dendrites, challenging the notion that only one to two RGCs innervate each relay cell. These findings force us to re-evaluate our understanding of subcortical visual circuitry.
- Nuclei-specific differences in nerve terminal distribution, morphology, and development in mouse visual thalamusHammer, Sarah; Carrillo, Gabriela Lizana; Govindaiah, Gubbi; Monavarfeshani, Aboozar; Bircher, Joseph S.; Su, Jianmin; Guido, William; Fox, Michael A. (BMC, 2014)Background: 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 nonretinal inputs that arise from cortical and subcortical sources. Although retinal and nonretinal 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. Results: 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 nonretinal 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. Conclusions: Taken together, these results reveal nuclei-specific differences in nerve terminal composition, distribution, and morphology in mouse visual thalamus. These results raise intriguing questions about the different functions of these nuclei in processing light-derived information, as well as differences in the mechanisms that underlie their unique, nuclei-specific development.