Role of long-range projecting inhibitory neurons in hippocampal network oscillations

In this study, I investigate the role that hippocampal inhibitory cells (intemeurons) have on the synchronization of oscillations between the two hemispheres of the hippocampus. My study focuses in particular on the ripple oscillations, because this network activity is highly synchronous between left and right hippocampus. My hypothesis is that a subset of hippocampal intemeurons might establish axonal connections from the hippocampal area in which the somata reside towards the contralateral side, hence regulating inter-hippocampal ripple discharges. I address this hypothesis injecting in one side of the hippocampus substance P fragment, a peptide that increases the activity of subsets of inhibitory neurons in rat hippocampus, and the antimalarial Quinine whose roles as gap-junction blocker has been well established by numerous publications. Simultaneous recording from both hippocampi are thus compared to investigate whether ipsilateral injected drugs affect hippocampal ripple activity recorded contralaterally. I found that ripple oscillations are indeed affected by injection of the abovementioned drugs: Quinine increases length and decreases Inter Ripple Interval (I.R.I.) in both injected and contralateral hippocampus; on the other hand, SP decreases the average amplitude of the ripple episode, but increases the duration of the ripple event. Most importantly, many of the perturbations observed were preserved between injected and contralateral hippocampus. Since the drugs I employed affect mainly inhibitory neurons, I propose that long-range projecting inhibitory neurons located in the injected hippocampus are responsible for carrying the drugs' effects to the contralateral hippocampus. In conclusion, my results seem to indicate that long-range projecting intemeurons are involved in transmitting ripple synchronization information across the two hippocampi.