Nucleus Accumbens Medium Spiny Neuron Subtypes Differentially Regulate Stress-Associated Alterations in Sleep...

Area of Science:

• Neuroscience
• Behavioral Science

Background:

• Stress is a key factor in major depression and PTSD, sharing symptoms like anxiety and sleep issues.
• Chronic stress in rodents mimics these symptoms, with individual differences in susceptibility and resilience.
• Nucleus accumbens neuroadaptations are linked to stress-induced behavioral changes, but their impact on sleep remains unclear.

Purpose of the Study:

• To investigate the role of nucleus accumbens medium spiny neurons (MSNs) in sleep regulation under stress.
• To determine how altering dopamine D1 receptor (D1-MSN) and dopamine D2 receptor (D2-MSN) activity affects sleep and stress susceptibility.

Main Methods:

• Chemogenetics (Designer Receptors Exclusively Activated by Designer Drugs - DREADDs) were used to selectively manipulate D1-MSN and D2-MSN activity in mice.
• Continuous sleep-wake data were collected using wireless transmitters over 20 days.
• Behavioral tests were conducted to assess stress susceptibility in parallel mouse cohorts.

Main Results:

• D1-MSNs selectively influence rapid eye movement (REM) sleep, while D2-MSNs affect slow-wave sleep (SWS).
• Combined D1-MSN inhibition and D2-MSN activation mimicked sleep changes seen in chronic social defeat stress.
• Altered D1-MSN function impacted stress susceptibility in social behavior tests, and elevated CREB in D1-MSNs induced stress-like REM sleep effects.

Conclusions:

• The nucleus accumbens plays a significant role in regulating sleep, in addition to motivational and emotional behaviors.
• Specific MSN populations within the nucleus accumbens have distinct roles in controlling different sleep stages.
• These findings offer a neural framework for understanding the comorbidity of key features in stress-related disorders.