Disrupted connectivity in the olfactory bulb-entorhinal cortex-dorsal hippocampus circuit is associated with recognition memory deficit in Alzheimer’s disease model

Abstract

Neural synchrony in brain circuits is the mainstay of cognition, including memory processes. Alzheimer's disease (AD) is a progressive neurodegenerative disorder that disrupts neural synchrony in specific circuits, associated with memory dysfunction before a substantial neural loss. Recognition memory impairment is a prominent cognitive symptom in the early stages of AD. The entorhinal–hippocampal circuit is critically engaged in recognition memory and is known as one of the earliest circuits involved due to AD pathology. Notably, the olfactory bulb is closely connected with the entorhinal–hippocampal circuit and is suggested as one of the earliest regions affected by AD. Therefore, we recorded simultaneous local field potential from the olfactory bulb (OB), entorhinal cortex (EC), and dorsal hippocampus (dHPC) to explore the functional connectivity in the OB-EC-dHPC circuit during novel object recognition (NOR) task performance in a rat model of AD. Animals that received amyloid-beta (Aβ) showed a significant impairment in task performance and a marked reduction in OB survived cells. We revealed that Aβ reduced coherence and synchrony in the OB-EC-dHPC circuit at theta and gamma bands during NOR performance. Importantly, our results exhibit that disrupted functional connectivity in the OB-EC-dHPC circuit was correlated with impaired recognition memory induced by Aβ. These findings can elucidate dynamic changes in neural activities underlying AD, helping to find novel diagnostic and therapeutic targets.

Modulation of entorhinal cortex–hippocampus connectivity and recognition memory following electroacupuncture on 3×Tg-AD model: Evidence from multimodal MRI and electrophysiological recordings

“…They are the earliest regions affected by AD, and the EC conveys spatial/contextual and object information to the hippocampus (van Strien et al, 2009;Knierim et al, 2014). Previous observations have revealed that coherent oscillatory activity in EC-Hip was correlated with object recognition memory performance (Salimi et al, 2022). Consistent with previous studies, the result in the present study has shown that EC and Hip are correlated with recognition memory performance.…”

“…Compelling evidence demonstrated that altered recognition memory in both cognitive impairment patients and animals is potentially associated with changes in regional spontaneous activities and neural connectivity, including the hippocampalcortex network (Matura et al, 2014;De Marco et al, 2017;Tanimizu et al, 2018;Salimi et al, 2022). Previous studies found that EA not only increased the neuronal activity of the hippocampus in mild cognitive impairment (MCI) patients but also enhanced the functional connections between brain regions (Tan et al, 2017).…”

Signatures for Viral Infection and Inflammation in the Proximal Olfactory System in Familial Alzheimer’s Disease

“…Taken together with a parallel body of literature indicating that early AD is characterized by smell loss 1-3 , amyloid deposition in the olfactory epithelium (OE), and olfactory sensory neuron (OSN) dysfunction 4, 5 , our study raises the possibility that viral infection of the OB/OT accelerates AD. Because sniff-induced beta and theta-coupled gamma oscillations generated in the OB are directionally coupled to the hippocampus 25-28 , smell loss would result in decreased hippocampal gamma oscillations that have been postulated to lead to neurodegeneration and cognitive decline 29-31 . These studies suggest that virus disruption of olfactory pathways can accelerate AD cognitive decline (Figure 4).…”

“…Because sniff-induced beta and theta-coupled gamma oscillations generated in the OB are directionally coupled to the hippocampus 13–16 , smell loss would result in decreased hippocampal gamma oscillations that have been postulated to lead to neurodegeneration and cognitive decline. 17–19 These studies suggest that alphaherpesvirus disruption of olfactory pathways can accelerate AD cognitive decline (Supplementary Figure 4).…”

Olfactory bulb stimulation mitigates Alzheimer’s-like disease progression

“…injection were carried out in accordance with our previous protocol. 28 Briefly, after anesthetizing, the animals were placed on the stereotaxic apparatus, and then the skull was exposed for finding the coordinates in the Paxinos atlas. Based on the reference points in the Paxinos atlas, we found the coordinates for OB (AP: 8.5 mm, ML: ± 1 mm, DV: − 1.5 mm), i.c.v.…”