Reinforcement of rat hippocampal LTP by holeboard training

Hippocampal long-term potentiation (LTP) can be dissociated in early-LTP lasting 4–5 h and late-LTP with a duration of more than 8 h, the latter of which requires protein synthesis and heterosynaptic activity during its induction. Previous studies in vivo have shown that early-LTP in the dentate gyrus can protein synthesis-dependently be transformed (reinforced) into late-LTP by the association of arousing novel environmental stimuli. Here we show that consolidation of spatial memory also reinforces early-LTP in the dentate gyrus. Both memory consolidation and LTP-reinforcement depend on protein synthesis. Four groups of animals were trained by five, seven, eight or 10 trials, respectively, to recognize a fixed pattern of baited holes. The last trial was performed 15 min after tetanus. Errors of long-term reference memory during the last trial were significantly decreased only in the eight- and 10-trial experimental groups compared to pseudo-trained animals. In correlation to this learning effect we found a reinforcement of early-LTP only in these experimental groups compared to controls. The data suggest that the synthesis of new proteins required for spatial reference-memory formation also contributes to LTP maintenance in the hippocampal dentate gyrus

Reduction of Hippocampal High-Frequency Activity in Wag/Rij Rats with a Genetic Predisposition to Absence Epilepsy

In temporal lobe epilepsy, high frequency oscillations serve as electroencephalographic (EEG) markers of epileptic hippocampal tissue. In contrast, absence epilepsy and other idiopathic epilepsies are known to result from thalamo-cortical abnormalities, with the hippocampus involvement considered to be only indirect. We aimed to uncover the role of the hippocampus in absence epilepsy using a genetic rat model of absence epilepsy (WAG/Rij rats), in which spike-wave discharges (SWDs) appear spontaneously in cortical EEG. We performed simultaneous recordings of local field potential from the hippocampal dentate gyrus using pairs of depth electrodes and epidural cortical EEG in freely moving rats. Hippocampal ripples (100–200 Hz) and high frequency oscillations (HFO, 50–70 Hz) were detected using GUI RIPPLELAB in MatLab (Navarrete et al., 2016). Based on the dynamics of hippocampal ripples, SWDs were divided into three clusters, which might represent different seizure types in reference to the involvement of hippocampal processes. This might underlie impairment of hippocampus-related cognitive processes in some patients with absence epilepsy. A significant reduction to nearly zero-ripple-density was found 4–8 s prior to SWD onset and during 4 s immediately after SWD onset. It follows that hippocampal ripples were not just passively blocked by the onset of SWDs, but they were affected by spike-wave seizure initiation mechanisms. Hippocampal HFO were reduced during the preictal, ictal and postictal periods in comparison to the baseline. Therefore, hippocampal HFO seemed to be blocked with spike-wave seizures. All together, this might underlie impairment of hippocampus-related cognitive processes in some patients with absence epilepsy. Further investigation of processes underlying SWD-related reduction of hippocampal ripples and HFO oscillations may help to predict epileptic attacks and explain cognitive comorbidities in patients with absence epilepsy