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Rostral intralaminar thalamic deep brain stimulation ameliorates memory deficits and dendritic regression in β-amyloid-infused rats

Abstract

Rostral intralaminar thalamic deep brain stimulation (ILN-DBS) has been shown to enhance attention and cognition through neuronal activation and brain plasticity. We examined whether rostral ILN-DBS can also attenuate memory deficits and impaired synaptic plasticity and protect glutamatergic transmission in the rat intraventricular β-amyloid (Aβ) infusion model of Alzheimer’s disease (AD). Spatial memory was tested in the Morris water maze (MWM), while structural synaptic plasticity and glutamatergic transmission strength were estimated by measuring dendritic spine densities in dye-injected neurons and tissue expression levels of postsynaptic density protein 95 (PSD-95) in medial prefrontal cortex (mPFC) and hippocampus. All these assessments were compared among the naïve control rats, AD rats, and AD rats with ILN-DBS. We found that a single rostral ILN-DBS treatment significantly improved MWM performance and reversed PSD-95 expression reductions in the mPFC and hippocampal region of Aβ-infused rats. In addition, ILN-DBS preserved dendritic spine densities on mPFC and hippocampal pyramidal neurons. In fact, MWM performance, PSD-95 expression levels, and dendritic spine densities did not differ between naïve control and rostral ILN-DBS treatment groups, indicating near complete amelioration of Aβ-induced spatial memory impairments and dendritic regression. These findings suggest that the ILN is critical for modulating glutamatergic transmission, neural plasticity, and spatial memory functions through widespread effects on distributed brain regions. Further, these findings provide a rationale for examining the therapeutic efficacy of ILN-DBS in AD patients.

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Acknowledgments

We are grateful to Professor Yu-Ru Kou and Dr. Ben S. Huang for discussion, comments, and English editing of the paper.

Funding

Tzu Chi University: TCIRP 104001-0, 104001-05, 107001-01, and 107001-04; Ministry of Science and Technology of Taiwan: 104-2320-B-320-001-MY3; 107-2320-B-320-006 and 108-2314-B-303-014.

Author information

1. Research project: A. conception: ST, SC, SL, GT, B. execution: ST, GT; 2. statistical analysis: A. design and execution: ST, B. review and critique: SC, SL, GT; 3. manuscript preparation: A. writing of the first draft: ST, B. review and critique: SC, GT. All authors read and approved the final manuscript.

Correspondence to Guo-Fang Tseng.

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Tsai, S., Chen, S., Lin, S. et al. Rostral intralaminar thalamic deep brain stimulation ameliorates memory deficits and dendritic regression in β-amyloid-infused rats. Brain Struct Funct (2020). https://doi.org/10.1007/s00429-020-02033-6

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Keywords

  • Cortical plasticity
  • Thalamus
  • Deep brain stimulation
  • Alzheimer’s disease