Disrupted connectivity in the olfactory bulb-entorhinal cortex-dorsal hippocampus circuit is associated with recognition memory deficit in Alzheimer\u2019s disease model

Morteza Salimi,Mohammad Javan,Farhad Tabasi,Kolsoum Dehdar,Maryam Abdolsamadi,Mohammad Reza Raoufy,Javad Mirnajafi-Zadeh,Milad Nazari,Samaneh Dehghan

doi:10.1038/s41598-022-08528-y

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.

Highlights

Neural synchrony in brain circuits is the mainstay of cognition, including memory processes
Our findings showed that Aβ pathology affected granule cell layer (GCL), glomerular layer (GLM), external plexiform layer (EPL), and mitral cell layer (MCL) containing glomerular, mitral, and tufted cells rather than the rest of the subregions
These results demonstrate that Aβ1-42 infusion results in Aβ plaque formation and neural loss, hallmarks of Alzheimer’s disease (AD) pathology in our region of interests (i.e., olfactory bulb (OB), entorhinal cortex (EC), and dorsal hippocampus (dHPC)), and confirm model induction

Summary

Introduction

Neural synchrony in brain circuits is the mainstay of cognition, including memory processes. Recognition memory impairment is a prominent cognitive symptom in the early stages of AD. 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-ECdHPC circuit during novel object recognition (NOR) task performance in a rat model of AD. 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. Two structures that are proposed affected in AD early stages are the entorhinal cortex (EC)[15] and hippocampus (HPC)[16], both pivotal for proper memory functions, notably, object r ecognition[17]. OB can be a key candidate for investigating early functional changes in the brain induced by AD pathology

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Conclusion