| First Author | Zhong P | Year | 2024 |
| Journal | J Alzheimers Dis | Volume | 98 |
| Issue | 3 | Pages | 1121-1131 |
| PubMed ID | 38489190 | Mgi Jnum | J:355489 |
| Mgi Id | MGI:7748854 | Doi | 10.3233/JAD-231413 |
| Citation | Zhong P, et al. (2024) Distinct and Convergent Alterations of Entorhinal Cortical Circuits in Two Mouse Models for Alzheimer's Disease and Related Disorders. J Alzheimers Dis 98(3):1121-1131 |
| abstractText | BACKGROUND: The impairment of neural circuits controlling cognitive processes has been implicated in the pathophysiology of Alzheimer's disease and related disorders (ADRD). However, it is largely unclear what circuits are specifically changed in ADRD, particularly at the early stage. OBJECTIVE: Our goal of this study is to reveal the functional changes in the circuit of entorhinal cortex (EC), an interface between neocortex and hippocampus, in AD. METHODS: Electrophysiological, optogenetic and chemogenetic approaches were used to examine and manipulate entorhinal cortical circuits in amyloid-beta familial AD model (5xFAD) and tauopathy model (P301S Tau). RESULTS: We found that, compared to wild-type mice, electrical stimulation of EC induced markedly smaller responses in subiculum (hippocampal output) of 5xFAD mice (6-month-old), suggesting that synaptic communication in the EC to subiculum circuit is specifically blocked in this AD model. In addition, optogenetic stimulation of glutamatergic terminals from prefrontal cortex (PFC) induced smaller responses in EC of 5xFAD and P301S Tau mice (6-month-old), suggesting that synaptic communication in the PFC to EC pathway is compromised in both ADRD models. Chemogenetic activation of PFC to EC pathway did not affect the bursting activity of EC neurons in 5xFAD mice, but partially restored the diminished EC neuronal activity in P301S Tau mice. CONCLUSIONS: These data suggest that 5xFAD mice has a specific impairment of short-range hippocampal gateway (EC to subiculum), which may be caused by amyloid-beta deposits; while two ADRD models have a common impairment of long-range cortical to hippocampal circuit (PFC to EC), which may be caused by microtubule/tau-based transport deficits. These circuit deficits provide a pathophysiological basis for unique and common impairments of various cognitive processes in ADRD conditions. |
