Lesion-induced sprouting promotes neurophysiological integration of septal and entorhinal inputs to granule cells in the dentate gyrus of rats.

Axonal sprouting of dentate gyrus (DG) afferents after entorhinal cortex (EC) lesion is a model preparation to assess lesion-induced functional reorganization in a denervated target structure. Following a unilateral EC lesion, the surviving contralateral entorhinal projection, termed the crossed temporodentate pathway (CTD), and the heterotypic septal input to the DG, the septodentate pathway (SD), undergo extensive axonal sprouting. We explored whether EC lesion alters the capacity of the SD pathway to influence CTD-evoked granule cell excitability in the DG. We recorded extracellular field excitatory postsynaptic potentials (fEPSPs) after CTD stimulation alone and paired SD-CTD stimulation. Male rats were given unilateral EC lesions or sham operations; evoked fEPSPs in the DG were recorded at 4-, 15-, and 90-days post-entorhinal lesion to assess functional reorganization of the CTD and SD pathways. We found significantly increased fEPSP amplitudes in cases with unilateral lesions compared to sham-operates at 15- and 90-days post lesion. Within each time point, paired SD-CTD stimulation resulted in significantly depressed fEPSP amplitudes compared to amplitudes evoked after CTD stimulation alone and this effect was solely seen in cases with EC lesion. In cases where granule cell discharge was observed, SD stimulation increased discharge amplitude elicited by the CTD stimulation at 90-days postlesion. These findings demonstrate that synaptic remodeling following unilateral cortical lesion results in a synergistic interaction between two established hippocampal afferents that is not seen in uninjured brains. This work may be important for models of neurodegenerative disease and neural injury that target these structures and associated hippocampal circuitry.

A large majority of awake hippocampal sharp-wave ripples feature spatial trajectories with momentum.

During periods of rest, hippocampal place cells feature bursts of activity called sharp-wave ripples (SWRs). Heuristic approaches have revealed that a small fraction of SWRs appear to "simulate" trajectories through the environment, called awake hippocampal replay. However, the functional role of a majority of these SWRs remains unclear. We find, using Bayesian model comparison of state-space models to characterize the spatiotemporal dynamics embedded in SWRs, that almost all SWRs of foraging rodents simulate such trajectories. Furthermore, these trajectories feature momentum, or inertia in their velocities, that mirrors the animals' natural movement, in contrast to replay events during sleep, which lack such momentum. Last, we show that past analyses of replayed trajectories for navigational planning were biased by the heuristic SWR sub-selection. Our findings thus identify the dominant function of awake SWRs as simulating trajectories with momentum and provide a principled foundation for future work on their computational function.