UC San Diego

The suprachiasmatic nucleus (SCN) of the hypothalamus is known as the master clock, which controls mammalian circadian rhythms. Located in the brain above the optic chiasm, the SCN entrains to daily environmental light cycles via innervations from the retina. Intrinsically photosensitive retinal ganglion cells (mRGCs), which express the photopigment melanopsin, send axonal projections down the retinohypothalamic tract (RHT). Each mRGC communicates with neurons in the SCN via boutons, small swellings along its axonal length filled with vesicles containing neuropeptides. The SCN consists of two morphologically distinct regions where synaptic connections of the RHT deliver light information: the core and the shell. In this study we reconstructed the connectome of the mRGC network in the shell and core regions of the SCN using the electron microscopy tag APEX2, and characterized differences in the structures of the two SCN regions using IMOD software to reconstruct 3D images of neurons. Quantification of synaptic strength between mRGCs and the SCN was evaluated by measuring the bouton density and average volume of mRGC synapses. We found that the average bouton volume of the mRGC contacts in the SCN shell are significantly larger than those in the SCN core however, mRGCs make fewer connections in the shell than the core. Reconstruction of the neuronal connections is necessary for the understanding of the flow of information from the retina to the SCN, and this understanding may aid and expedite the development of therapies targeting disruptions in the mammalian circadian rhythms.