Compromised synaptic signal from prefrontal cortex to mediodorsal thalamus in Alzheimer's disease models and its rescue by kinase inhibitors - PubMed
5 days ago
- #Alzheimer's disease
- #Tau kinases
- #Optogenetics
- The study investigates synaptic signals from the prefrontal cortex (PFC) to the mediodorsal thalamus (MD) in Alzheimer's disease (AD) models.
- Optogenetic experiments showed stronger synaptic currents in MD compared to neighboring thalamic areas, indicating prominent PFC-to-MD signaling.
- Two AD mouse models (P301S Tau and 5xFAD) exhibited altered short-term depression (STD) in PFC-to-MD synaptic responses.
- Tau mice showed reduced ChR2 expression in MD axon terminals, suggesting compromised axonal transport.
- Inhibition of kinases SGK1 and GSK3β normalized STD in Tau mice but not in 5xFAD mice, indicating tau-related pathology.
- The findings suggest that synaptic connectivity in the PFC-to-MD pathway is disrupted in AD, possibly due to tau kinase-induced axonal transport issues.