Synaptic plasticity and novelty-mediated shifts in hippocampal mnemonic processing

Hippocampal mnemonic function is thought to require long-term potentiation (LTP), long-term depression (LTD) and novelty-mediated shifts in encoding and retrieval states to preserve old memories during new learning. These studies examine unexplored aspects of these phenomena. Given homosynaptic LTD is rarely reported at perforant path-dentate gyrus synapses in vivo, we investigated dentate LTD in intact animals following low frequency stimulation of the lateral perforant path (LPP) or medial perforant path. Although LTD rarely occurred following acute electrode implantation in anesthetized rats, LTD exhibited a pathway-specific prevalence at LPP-DG synapses in both freely moving and anesthetized rats with previously implanted electrodes, suggesting surgery-related tissue trauma influence LTD induction. In addition, some memory functions are mediated by entorhinal layer III medial temporoammonic (mTA) projections, thus we characterized in vivo mTA-CA1 responses and LTP in freely moving animals. Medial TA-CA1 slopes exhibited an input specific LTP in freely moving rats that endured, on average, two weeks. These data indicate mTA-CA1 responses can be isolated in vivo and demonstrate robust LTP. Finally, novelty detection and Type 2 theta rhythm are suggested to regulate the dynamic activation of the "tri-synaptic loop" during encoding, thus we examined the effects of Type 2 theta rhythm on the relative timing of DG and CA3 discharge. In non-theta conditions of pentobarbital anesthesia or home cage exposure, rats exhibited CA3 discharge that preceded DG discharge. Theta conditions, such as urethane and novelty exploration, enabled DG discharge to precede CA3 discharge or produced phasic observations of near-synchronous DG and CA3 spikes, suggesting theta rhythm promotes shifts in spike latency which may facilitate coincidence detection and spike timing dependent LTP of PP-CA3 and mossy fiber-CA3 synaptic activity. Although the hippocampal formation is implicated in novelty detection, the structures involved have not been determined. Our examinations of the contribution of mTA-CA1 synapse in novelty P300 evoked potentials revealed no consistent correlation between the polarity of the mTA-CA1 response and P300 recordings in area CA1, suggesting hippocampal novelty P300 evoked potentials are generated at an alternate site.