Selective weakening of population-coupled synaptic activity in vivo in a mouse model of amyloid-beta pathology - PubMed
4 days ago
- #Alzheimer's disease
- #synaptic dysfunction
- #GABAergic neurons
- Synaptic dysfunction in Alzheimer's disease (AD) may drive synapse loss and cognitive impairment.
- Study investigates AD-related synaptic dysfunction during early-stage amyloidosis in AppNL-G-F mice.
- Findings include reduced presynaptic GABAergic proteins at c-Fos-positive excitatory neurons and increased calcium-mediated activity at excitatory and inhibitory neuronal assemblies.
- In vivo imaging shows reduced density and calcium-mediated activity of GABAergic axonal boutons.
- Reduced synaptic activity is focused at GABAergic boutons strongly coupled to population activity in the amyloid microenvironment.
- Selective weakening of population-coupled synaptic activity also occurs in excitatory dendritic spines.
- Spatial transcriptomics reveals differential gene expression in parvalbumin-positive inhibitory neurons, associated with downregulated GABAergic synaptic transmission at early stages.
- Proposal that early-stage AD-related synaptic pathophysiology is focused at population-coupled synapses, with abnormal synaptic processing in parvalbumin-positive interneurons.