Altered corticostriatal synchronization associated with compulsive-like behavior in APP/PS1 mice

Area of Science:

• Neuroscience
• Alzheimer's Disease Research
• Behavioral Neuroscience

Background:

• Mild behavioral impairment (MBI), including compulsive behaviors, can be an early indicator of Alzheimer's disease (AD).
• The neural underpinnings of MBI in the early stages of AD are not well understood.
• APP/PS1 mouse models are frequently used to study AD pathogenesis.

Purpose of the Study:

• To investigate the neural mechanisms underlying early behavioral changes in a mouse model of Alzheimer's disease.
• To examine the role of corticostriatal circuits in mild behavioral impairment.
• To identify specific neuronal and molecular alterations associated with presymptomatic AD-like behaviors.

Main Methods:

• Assessment of obsessive-compulsive disorder (OCD)-like behaviors in 3-5-month-old APP/PS1 mice.
• Electrophysiological recordings (Local Field Potentials - LFPs) in the prefrontal cortex (PFC) and striatum (Str).
• Measurement of parvalbumin-positive (PV) interneuron numbers and neurotransmitter receptor levels (GABA, glutamate).

Main Results:

• APP/PS1 mice exhibited OCD-like behaviors at 3-5 months of age.
• Reduced numbers of PV interneurons and decreased high gamma (γhigh) oscillations in the striatum.
• Altered β-γhigh coupling, increased striatal projection neuron (SPN) firing rates, and decreased corticostriatal coherence.
• Reduced levels of GABA_B receptors were observed, correlating with behavioral changes.

Conclusions:

• Mild behavioral impairment, characterized by OCD-like behaviors, manifests early (3-5 months) in APP/PS1 mice.
• Altered synchronization and impaired communication within corticostriatal circuits may underlie these early AD-related behavioral phenotypes.
• Changes in specific GABAergic and glutamatergic receptor levels are associated with presymptomatic AD-like behaviors.