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

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 (Aß) showed a significant impairment in task performance and a marked reduction in OB survived cells. We revealed that Aß 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 Aß. These findings can elucidate dynamic changes in neural activities underlying AD, helping to find novel diagnostic and therapeutic targets.

ACC-BLA functional connectivity disruption in allergic inflammation is associated with anxiety.

Allergic asthma is a chronic inflammatory respiratory disease. Psychiatric disorders, including anxiety are associated with poorer treatment response and disease control in asthmatic patients. To date, there is no experimental evidence describing the role of peripheral inflammation on the oscillatory activities in the anterior cingulate cortex (ACC) and basolateral amygdala (BLA), two major brain structures modulating anxiety. In the present work we evaluated lung and brain inflammatory responses, anxiety-like behavior, in association with oscillatory features of the ACC-BLA circuit in an animal model of allergic inflammation. Our data showed that allergic inflammation induced anxiety-like behavior and reactivation of microglia and astrocytes in ACC and BLA. Allergic inflammation also enhanced neuronal activities and functional connectivity of the ACC-BLA circuit which were correlated with the level of anxiety. Together, we suggest that disruption in the dynamic oscillatory activities of the ACC-BLA circuit, maybe due to regional inflammation, is an underlying mechanism of allergic asthma-induced anxiety-like behavior. Our findings could pave the way for better understanding the neuro-pathophysiology of the psychiatric disorders observed in asthmatic patients, possibly leading to develop novel treatment strategies.