Reward and aversion processing by input-defined parallel nucleus accumbens circuits in mice.

Area of Science:

• Neuroscience
• Molecular Biology
• Behavioral Science

Background:

• The nucleus accumbens (NAc) plays a key role in reward seeking and negative emotion processing.
• The specific cellular and circuitry mechanisms underlying these opposing functions are not fully understood.

Purpose of the Study:

• To elucidate the distinct neural circuits within the NAc that mediate opposing behaviors like reward and aversion.
• To investigate the role of afferent-specific NAc pathways in reinforcement and withdrawal.

Main Methods:

• Utilized AAV1-mediated anterograde transsynaptic tagging in mice.
• Investigated NAc neurons receiving inputs from the basolateral amygdala (NAc^BLA) and paraventricular thalamus (NAc^PVT).
• Examined the effects of silencing specific NAc pathways on reward seeking and opiate withdrawal behaviors.

Main Results:

• NAc^BLA neurons disinhibit ventral tegmental area (VTA) dopamine neurons, promoting positive reinforcement.
• NAc^PVT neurons innervate lateral hypothalamus (LH) GABAergic neurons, mediating aversion.
• Silencing NAc^BLA impaired reward seeking; silencing NAc^PVT or the NAc^PVT→LH pathway abolished opiate withdrawal aversions.

Conclusions:

• The NAc exhibits distinct, afferent-specific circuit architectures for controlling reward and aversion.
• Identified specific pathways (NAc^BLA→VTA and NAc^PVT→LH) involved in opposing motivated behaviors.