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EN
Deep brain stimulation (DBS) is a neuromodulation method that modulates neuronal activity. A trend in the treatment of Alzheimer’s disease (AD) is targeting key points of neural circuits with DBS. Here, we explored the effects of DBS targeted to the entorhinal cortex (EC) on neurons in the hippocampal CA1 in a mouse model of preclinical AD. Specifically, we recorded field potential signals from CA1 in preclinical AD mice after DBS of the EC (1 h/day for 21 days of 100 lA, 90 ls, 10 Hz, biphasic square wave pulse) with in-vivo electrophysiology and evaluated corresponding changes in behavior with the open field task and Morris water maze (MWM) task. We also assessed changes in pathological markers and neurogenesis in the hippocampus with immunohistological staining. DBS of the EC increased theta and gamma power and modulated theta in the high gamma band (50-100 Hz) in preclinical AD mice. After DBS of the EC, these mice performed better in the MWM task and exhibited reduced deposition of beta-amyloid and neuronal changes including significant increases in proliferating neurons and immature neurons. This is the first study to target the EC with DBS and analyze resulting neural oscillations in the hippocampal CA1 in a model of preclinical AD. The findings support the use of DBS as a potential treatment for AD.
EN
This paper examines the spike-timing-dependent plasticity (STDP) at the synapses of the medial entorhinal cortex (EC) and the dentate gyrus (DG) in the hippocampus. The medial and lateral ECs respectively convey spatial and non-spatial information to the hippocampus, and the DG of the hippocampus integrates or binds them. There is a recurrent neuronal network between the EC and the hippocampus called the EC-hippocampus loop. A computational study has shown that using this loop and STDP phenomena at the recurrent EC synapse, sequential learning can be accomplished. But the STDP functions at the synapses of the EC and DG have not yet been studied by neurophysiological experiments. Experiments on STDP phenomena were performed in rats. The STDP function was asymmetrical in the EC synapse and symmetrical in the DG. The medial EC mainly processes the time-series signals for spatial information about visual landmarks when a rat is running in an environment, the lateral EC processes their features, and the DG binds or integrates the information on the positions and features of the landmarks. Thus, the EC-hippocampus loop processes sequential learning of spatial and non-spatial information in parallel, and the DG binds or integrates the two kinds of signals. A system based on this biological phenomenon could have similar characteristics of parallel processing of object features and positions, and their binding.
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