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Signal Attenuation as a Rat Model of Obsessive Compulsive Disorder
Published on: January 9, 2015
Altered corticostriatal synchronization associated with compulsive-like behavior in APP/PS1 mice
Yi-Gang Peng1, Ping-Jing Cai1, Jian-Hang Hu1
1School of Life Sciences, South China Normal University, Guangzhou 510631, China.
Abstract:
Mild behavioral impairment (MBI), which can include compulsive behavior, is an early sign of Alzheimer's disease (AD), but its underlying neural mechanisms remain unclear. Here, we show that 3-5-month-old APP/PS1 mice display obsessive-compulsive disorder (OCD)-like behavior. The number of parvalbumin-positive (PV) interneurons and level of high gamma (γhigh) oscillation are significantly decreased in the striatum of AD mice. This is accompanied by enhanced β-γhigh coupling and firing rates of putative striatal projection neurons (SPNs), indicating decorrelation between PV interneurons and SPNs. Local field potentials (LFPs) simultaneously recorded in prefrontal cortex (PFC) and striatum (Str) demonstrate a decrease in γhigh-band coherent activity and spike-field coherence in corticostriatal circuits of APP/PS1 mice. Furthermore, levels of GABAB receptor (GABABR), but not GABAA receptor (GABAAR), and glutamatergic receptors, were markedly reduced, in line with presymptomatic AD-related behavioral changes. These findings suggest that MBI occurs as early as 3-5 months in APP/PS1 mice and that altered corticostriatal synchronization may play a role in mediating the behavioral phenotypes observed.
Insights
Early Alzheimer's disease signs, like compulsive behavior, are linked to brain changes in mice. Researchers found altered neural activity and receptor levels in young APP/PS1 mice, suggesting early corticostriatal circuit dysfunction.
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 GABAB 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.
