Sex differences in mouse infralimbic cortex projections to the nucleus accumbens shell

Area of Science:

• Neuroscience
• Behavioral Neuroscience
• Neurobiology

Background:

• The nucleus accumbens (NAc) plays a crucial role in motivation and reward processing.
• Glutamatergic projections from the infralimbic cortex (ILC) to the NAc shell (NAcSh) are vital for reward-seeking behavior.
• Sex differences in motivational circuitry may explain differential vulnerability to substance use disorders.

Purpose of the Study:

• To investigate sex differences in the ILC-NAcSh circuitry's role in reward-seeking behavior using optogenetics.
• To explore how these differences manifest in response to varying stimulation frequencies and durations.

Main Methods:

• Utilized an optogenetic self-stimulation task in mice to measure reward-seeking.
• Performed ex vivo electrophysiological recordings of NAcSh neurons.
• Assessed optogenetically evoked potentials and intrinsic excitability of medium spiny neurons (MSNs).

Main Results:

• Females demonstrated greater reward-seeking behavior and photostimulation compared to males.
• Increased optogenetic stimulation frequency amplified female reward-seeking more than male.
• Male NAcSh slices showed greater evoked potentials, while female MSNs exhibited higher intrinsic excitability.

Conclusions:

• Significant sex differences exist in ILC-NAcSh circuit-driven motivated behavior.
• Heightened intrinsic excitability in female NAcSh MSNs underlies their enhanced reward-seeking.
• These findings contribute to understanding sex-based differences in motivation and addiction vulnerability.