The dynamic impairment of synaptic transmission in the PCx-IL engram circuit contributes to early olfactory memory decline in Alzheimer's disease - PubMed
5 hours ago
- #Alzheimer's Disease
- #Synaptic Transmission
- #Olfactory Memory
- Olfactory dysfunction is an early sign of Alzheimer's disease (AD), but the underlying neural circuit mechanisms are unclear.
- Functional connectivity between the piriform cortex (PCx) and infralimbic cortex (IL) is impaired in early mild cognitive impairment (MCI) stages of AD, as shown by fMRI.
- Optogenetic stimulation of IL-projecting PCx engram neurons improved olfactory memory retrieval in 5xFAD mouse models.
- Single-cell RNA sequencing revealed increased glutamate expression and impaired synaptic function in IL engram cells in AD.
- Dynamic impairment of AMPA receptor-associated synaptic transmission in the PCx-IL engram circuit contributes to early olfactory memory decline.
- Optical long-term potentiation (LTP) restored synaptic transmission in this circuit and prevented olfactory memory decline, suggesting a therapeutic target.