Nature Communications: Revealing a new mechanism by which the brain processes parallel circuits in the nucleus accumbens for reward and disgust

The motivation of animal behavior can be simply summarized as "seeking advantage and avoiding harm"
.
People pursue things that make themselves happy - such as food, games, music, etc.
, which can prompt the brain to secrete dopamine, bringing about the so-called "happy" feeling; And people will subconsciously avoid things they feel disgusted, such as hunger, danger, pain, etc
.
It should be pointed out that this avoidance behavior is an important reason why
most addicted patients cannot tolerate strong withdrawal symptoms and then fall into drug relapse.

Multiple brain regions are involved in regulating these processes, including the ventral tegmental area (VTA), nucleus accumbens (NAc), basolateral amygdala (BLA), and parathalamic nucleus (PVT).

The nucleus accumbens is regarded as the center for processing reward and disgust information, and is the brain area
that research focuses on.
NAc is mainly composed of
GABAergic medium-sized multispinous neurons (MSNs).
According to the different dopamine receptors expressed, MSN is divided into D1 and D2 type neurons
.
Previous studies have attributed the regulation of reward and disgust behavior to the difference between D1 and D2 neurons, but recent studies have shown that both D1- and D2- neurons can be involved in regulating reward and disgust behavior
.
Unlike other glutamate inputs projected to NAc, the PVT→NAc pathway was found to regulate the aversion effects
associated with morphine withdrawal.
So, can the functional units of the nucleus accumbens that regulate reward and disgust behaviors, respectively, be defined according to the specific upstream and downstream circuits of neurons?

Recently, the team of Zhu Yingjie, a researcher at the Shenzhen Institute of Advanced Technology of the Chinese Academy of Sciences, published research results in Nature Communications, revealing that the two parallel loops of the nucleus accumbens regulate reward and disgust respectively
.
The researchers used the AAV1-cre virus to label NAc neurons (NAcBLA) that received BLA projections and NAc neurons (NAcPVT) that received PVT projections, respectively, and found that they were two different groups of cells
.
The research team used optogenetics to activate NAcBLA and NAcPVT neurons and found that they mediate reward and disgust
, respectively.
Through neural tracing and patch-clamp electrophysiological recordings, it has been proved that NAcBLA neurons release the inhibition of dopamine neurons by projecting to GABAergic neurons of VTA, thereby promoting the release of dopamine mediated reward effects, while NAcPVT neurons mediate the disgust process
through GABAergic neurons projected to the lateral hypothalamus (LH).
Studies have shown that inactivating NAcBLA neurons causes mice to lose interest in gastronomy; Inactivated NAcPVT neurons effectively relieved opioid withdrawal symptoms
.

The study provides a new perspective on the loop in which nucleus accumbens (NAc) neurons encode reward and disgust, answering why different glutamate inputs mediate opposite behaviors
in the nucleus accumbens.
The results of this research will help promote in-depth research on the prevention and treatment of diseases related to reward and aversion, such as regulating the NAcPVT circuit to treat addiction and regulating the NAcBLA circuit to intervene in depression
.

The research work was supported
by the National Natural Science Foundation of China, Science and Technology Innovation 2030 - "Brain Science and Brain-like Research" Major Project, Guangdong Provincial Key Laboratory of Brain Connection Atlas, Shenzhen-Hong Kong Brain Science Innovation Research Institute and Shenzhen Science and Technology Innovation Commission.

NAcBLA neurons and NAcPVT neurons project to different downstream brain regions, respectively