A2A-Positive Neurons in the Nucleus Accumbens Core Regulate Effort Exertion

Area of Science:

• Neuroscience
• Behavioral Neuroscience
• Reward System

Background:

• The nucleus accumbens (NAc) is implicated in regulating effort-based decision-making.
• Specific neuronal populations within the NAc and their roles in effort regulation remain poorly understood.

Purpose of the Study:

• To investigate the distinct roles of direct pathway spiny projection neurons (dSPNs) and indirect pathway spiny projection neurons (iSPNs) in the NAc core in effort regulation.
• To determine if NAc core neuronal activity can bidirectionally control effort exertion.

Main Methods:

• Utilized an operant effort regulation task in male and female mice.
• Employed optogenetics to manipulate the activity of dSPNs (D1+) and iSPNs (A2A+) in the NAc core.
• Measured lever pressing as an indicator of effort exertion.

Main Results:

• Activation of NAc core dSPNs reduced lever pressing, independent of effort level, by inducing competing behaviors like gnawing.
• Activation of NAc core iSPNs reduced lever pressing in an effort-dependent manner, with greater reductions at higher effort requirements.
• Inhibition of NAc core iSPN output led to increased effort exertion.

Conclusions:

• The indirect pathway output from the NAc core plays a critical role in effort regulation.
• NAc core iSPN activity can bidirectionally control the amount of effort exerted for a reward.