EP 28. Fornix DBS enhances long-term spatial memory independent of hippocampal neuroplasticity

Abstract

Deep brain stimulation (DBS) of the fornix can restore memory functions in animals with experimental dementia. We have shown that one potential underlying mechanism is the enhanced release of acetylcholine in the hippocampus. Another suggested mechanism of action is neuronal plasticity. Here, we have tested the hypothesis that acute fornix DBS can have long-term beneficial effects on memory by enhancing histological parameters of neuronal and synaptic plasticity. Rats were implanted with bilateral electrodes at the site of the fornix and received DBS at 100 Hz, 100 μA and 100 μs pulse width for 4 h. Three days after stimulation, rats received BrdU injections twice daily for a period of 3 days. After 5 weeks, fornix DBS and sham rats were tested in the water maze task. Probe trials were given after 1 h and 48 h. About 6.5 weeks after DBS, rats were sacrificed and their brains processed for BrdU/NeuN, p-CREB or synaptophysin immunohistochemistry. Fornix DBS rats visited the target annulus more frequently than sham rats in the probe trial with 1 h delay. We did not find any differences for the number of double-labelled BrdU/NeuN or p-CREB cells for fornix DBS rats when compared to sham. Synaptophysin-immunoreactive presynaptic boutons, however, were significantly decreased in the CA1 and CA3 subfield of the hippocampus for fornix DBS rats when compared to sham. Fornix DBS enhances long-term spatial memory independent of the neuroplasticity markers, which were used in the present study. An interesting finding is the decrease in the synaptic-neuroplasticity marker, which might suggest a long-term depression related mechanism.