Abstract
Chronic cerebral hypoperfusion (CCH) is considered a preclinical condition of mild cognitive impairment and thought to precede dementia. However, as the principal cholinergic source of hippocampus, whether the septo-hippocampal neurocircuit was impaired after CCH is still unknown. In this study, we established the CCH rat model by bilateral common carotid artery occlusion (2VO). Under anesthesia, the medial septum (MS) of rats was stimulated to evoke the field excitatory post-synaptic potential (fEPSP) in the pyramidal cell layer of dCA1. Consequently, we observed decreased amplitude of fEPSP and increased paired-pulse ratio (PPR) after 8-week CCH. After tail pinch, we also found decreased peak frequency and shortened duration of hippocampal theta rhythm in 2VO rats, indicating the dysfunction of septo-hippocampal neurocircuit. Besides, by intracerebroventricularly injecting GABAergic inhibitor (bicuculline) and cholinergic inhibitors (scopolamine and mecamylamine), we found that CCH impaired both the pre-synaptic cholinergic release and the post-synaptic nAChR function in MS–dCA1 circuits. These results gave an insight into the role of CCH in the impairment of cholinergic MS–dCA1 neurocircuits. These findings may provide a new idea about the CCH-induced neurodegenerative changes.
Highlights
The integrity of basal forebrain–hippocampal neurocircuit is essential for the regulation of spatial and episodic memory (Ballinger et al, 2016)
To investigate whether Chronic cerebral hypoperfusion (CCH) could induce the dysfunction of the septo-hippocampal neurocircuit, we first evaluated the basic electrophysiological properties of the medial septum (MS)–dCA1 neurocircuit in vivo
CCH is considered to be the preclinical stage of mild cognitive impairment (Du et al, 2017); and it has already been proved to participate in the β-amyloid deposition, tau phosphorylation, neuronal death, impairment of hippocampal pre-synaptic plasticity, and theta oscillation in rats (Ai et al, 2013; Sun et al, 2015; Liu et al, 2016; Chen et al, 2017; Li et al, 2019; Yan et al, 2020)
Summary
The integrity of basal forebrain–hippocampal neurocircuit is essential for the regulation of spatial and episodic memory (Ballinger et al, 2016). Cholinergic Dysfunction in CCH Rats and retrograde labeling techniques, it has been found that, in 5XFAD mice, the degeneration of nerve fibers in the basal forebrain–hippocampus loop is earlier than the death of neurons (Kim et al, 2019). These studies suggest that impairment of the basal forebrain–hippocampal neurocircuit may be an early indicator of AD occurrence.
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