Figure 6

Schematic illustration of proposed mechanism for transhemispheric loop required for hippocampal progressive ADs. (a) Repetitive unilateral optogenetic stimulation leads to progressive increase in excitability of the local network, as evidenced by increased number of spontaneous LFPs during the stimulation train (ipsilateral s-LFPs, Fig. 2). These spontaneous LFPs spread to the contralateral hippocampus (red arrow), activating the contralateral dentate gyrus (contralateral s-LFPs, Fig. 4h), thus creating a transhemispheric feedback loop (black arrow) leading to progressive intensification of ADs bilaterally. Purple cells denotes increased activity indicated by Fos or LFP recordings. (b) If the contralateral hippocampus is inhibited, such as via hM4D-expressing neurons (located mainly in DG and CA3, orange) of CaMKIIa-ChR2 animals by CNO IP injection (green), feed-forward still exists (red arrow), while the feedback loop is selectively and temporarily disrupted (dashed arrow) and progressive intensification of ADs is halted.