Large-scale network activity and circuit connections in the developing mouse hippocampus

Developing neuronal circuits have many interesting properties; understanding the development process can give us insights on functioning of complex adult neural circuits. One of major features of immature neural circuits is the spontaneous activity, which has also been considered a driving force of circuit maturation. Giant Depolarizing Current (GDP) is the major spontaneous activity at single neuron level of developing hippocampus. What is missing, however, is whether hippocampus has large scale network level spontaneous activity that precedes the formation of mature hippocampal circuits, i.e. unidirectional trisynaptic flow. In chapter 1 of this study, we use Voltage Sensitive Dye Imaging to investigate the initiation and propagation of global network activity (GNA) in developing hippocampus. GNA originates in distal CA3 and propagates both forward to CA1 and backward to DG. Single-cell and local field potential recording confirmed GNA is closely related to neuronal activation. Further, enhancement of local circuit connections to excitatory pyramidal neurons occurs over the same time course as GNA. Thus Bi-directional GNA precedes the maturation of the mouse hippocampal circuit, and it is correlated to maturation of functional circuit connections. To further understand the underlying pathway for back-projection from CA3 to DG in the developing hippocampus, in the study of chapter 2, we use laser scanning photostimulation technique to map synaptic circuit development of mossy cells. We observed major regional sources of circuit excitation and inhibition to hilar mossy cells were changed from CA3 to DG during development. The excitatory back projection from CA3 to mossy cell were greatly reduced in adult hippocampus. Thus, hilar mossy cells can play important role in circuit signal back-propagation from CA3 to DG. In chapters 3 and 4, we demonstrate an innovative technology which automatically detects and extracts EPSC and IPSC events in electrophysiological recording. We also present our GPU based computing system and our modification of the previous technology to utilize the power of GPU computing. GPU computation could greatly improve the speed of computation while retaining data precision. Taken together, my dissertation studies contribute new and important knowledge to the field of hippocampus circuit studies, using our newly developed techniques