@article {ShiENEURO.0370-18.2019, author = {Yulin Shi and Steven F. Grieco and Todd C. Holmes and Xiangmin Xu}, title = {Development of local circuit connections to hilar mossy cells in the mouse dentate gyrus}, elocation-id = {ENEURO.0370-18.2019}, year = {2019}, doi = {10.1523/ENEURO.0370-18.2019}, publisher = {Society for Neuroscience}, abstract = {Hilar mossy cells in the dentate gyrus (DG) shape the firing and function of the hippocampal circuit. However, the neural circuitry providing afferent input to mossy cells is incompletely understood, and little is known about the development of these inputs. Thus, we used whole-cell recording and laser scanning photostimulation (LSPS) to characterize the developmental trajectory of local excitatory and inhibitory synaptic inputs to mossy cells in the mouse hippocampus. Hilar mossy cells were targeted by visualizing non-red fluorescent cells in the dentate hilus of GAD2-Cre; Ai9 mice, which expressed tdTomato in GAD+ neurons, and were confirmed by post hoc morphological characterization. Our results show that at postnatal days 6-7 (P6-7), mossy cells received more excitatory input from neurons in the proximal CA3 versus those in the DG. In contrast, at P13-14 and P21-28, the largest source of excitatory input originated in DG cells, while the strength of CA3 and hilar inputs declined. A developmental trend was also evident for inhibitory inputs. Overall inhibitory input at P6-7 was weak, while inhibitory inputs from the DG cell layer and the hilus predominated at P13-14 and P21-28. The strength of local DG excitation and inhibition to mossy cells peaked at P13-14 and decreased slightly in older P21-28 mice. Together, these data provide new detailed information on the development of local synaptic connectivity of mossy cells, and suggests mechanisms through which developmental changes in local circuit inputs to hilar mossy cells shape their physiology and vulnerability to injury during postnatal periods.Significance statement Mossy cells of the dentate gyrus (DG) have been implicated in hippocampal circuits regulating pattern separation, an important function attributed to the DG. However, physiological inputs regulating mossy cell activity are incompletely understood. Here, we show that sources of both excitatory and inhibitory inputs arise developmentally. Our results suggest that excitatory inputs from the DG and local inhibitory inputs are well-positioned to powerfully sculpt receptive fields in mature mossy cells.}, URL = {https://www.eneuro.org/content/early/2019/03/07/ENEURO.0370-18.2019}, eprint = {https://www.eneuro.org/content/early/2019/03/07/ENEURO.0370-18.2019.full.pdf}, journal = {eNeuro} }