Fig. 1.

Graphical representation of the timeline of experiment and anatomy of the medial septum-hippocampal spatial circuit anatomy. A. A viral vector expressing channelrhodopsin (ChR2) was injected into the medial septum (MS) at postnatal (P) day 7. Following a series of 25 flurothyl-induced seizures between P9-P13, pups were then subjected to intermittent MS-induced theta activity of 7 Hz during the critical period (P21-P25). Half the pups with early-life seizures (ELS) and controls (CTL) received either active blue light (BL) or inert yellow light (YL) during the critical period of spatial cognition. The rats were then studied as adults in the active avoidance task and had EEGs done. B. MS (pink) and ventral hippocampus (light green) in three-dimensional view. Red arrows represent horizontal plane and green and blue arrows represent vertical plane. Circled A and P denote anterior and posterior directions. Bottom: Two-dimension coronal view of interconnections of MS and hippocampus. In the MS, cholinergic (yellow circle), glutamatergic (pink circle) and GABAergic neurons (blue circle) form a highly interconnected local network. Neurons of these three classes project to glutamatergic pyramidal neurons and different subsets of GABAergic neurons in CA1. GABAergic neurons project back to the MS and form a feedback loop between the two anatomical distant brain regions.