Dysfunction of Somatostatin-Positive Interneurons Associated with Memory Deficits in an Alzheimer's Disease Model.
Neuron
; 92(1): 114-125, 2016 Oct 05.
Article
in En
| MEDLINE
| ID: mdl-27641495
ABSTRACT
Alzheimer's disease (AD) is characterized by cognitive decline and neuronal network dysfunction, but the underlying mechanisms remain unknown. In the hippocampus, microcircuit activity during learning and memory processes is tightly controlled by O-LM interneurons. Here, we investigated the effect of beta-amyloidosis on O-LM interneuron structural and functional connectivity, combining two-photon in vivo imaging of synaptic morphology, awake Ca2+ imaging, and retrograde mono-transsynaptic rabies tracing. We find severely impaired synaptic rewiring that occurs on the O-LM interneuron input and output level in a mouse model of AD. Synaptic rewiring that occurs upon fear learning on O-LM interneuron input level is affected in mice with AD-like pathology. This process requires the release of acetylcholine from septo-hippocampal projections. We identify decreased cholinergic action on O-LM interneurons in APP/PS1 mice as a key pathomechanism that contributes to memory impairment in a mouse model, with potential relevance for human AD.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Somatostatin
/
Alzheimer Disease
/
Interneurons
/
Memory Disorders
/
Neuronal Plasticity
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
Neuron
Journal subject:
NEUROLOGIA
Year:
2016
Document type:
Article
Affiliation country: