Development of Local Circuit Connections to Hilar Mossy Cells in the Mouse Dentate Gyrus

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 that expressed tdTomato in GAD+ neurons, and were confirmed by post hoc morphological characterization. Our results show that at postnatal day (P)6-P7, mossy cells received more excitatory input from neurons in the proximal CA3 versus those in the DG. In contrast, at P13-P14 and P21-P28, 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-P7 was weak, while inhibitory inputs from the DG cell layer and the hilus predominated at P13-P14 and P21-P28. The strength of local DG excitation and inhibition to mossy cells peaked at P13-P14 and decreased slightly in older P21-P28 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.