Scenes reactivate novel mechanisms of addictive memory through inhibition-desuppression neural circuits

Recently, the research work of Professor Zheng Ping's research group of the Institute of Brain Sciences/State Key Laboratory of Medical Neurobiology of Fudan University has discovered a new mechanism
by which scenes reactivate addictive memory through the inhibition-desuppression neural circuit.
The findings were published online in Nature Communications on January 5
, 2023.
Sheng Huan, Lei Chao and Yuan Yu, graduate students supervised by Zheng Ping, are co-first authors, and Zheng Ping, Lai Bin and Chen Ming are co-corresponding authors
.

Drug addiction is a serious social problem
.
There are a variety of ways to effectively detoxify addicts and relieve the symptoms of
addiction.
However, even if detoxification is long, there are still many factors that can lead to drug relapse, one of the important factors is that when the detoxified person enters a scene where withdrawal symptoms have occurred, this scene can reactivate the addictive memory, leading to drug relapse
.
Therefore, studying the neural mechanism of scene activation of addictive memory is of great significance
for effective intervention in drug relapse.

Zheng Ping's research group put the drug addict rat in two boxes with different scenes, and then made the addict rat suddenly withdraw from drugs in one box, causing it to produce painful withdrawal symptoms, forming a painful memory of drug withdrawal, and linking this memory with the scene it was in, and then putting the mouse in this scene again, it can reactivate the painful memory of drug withdrawal, so that it dislikes this scene and "escapes" from this box
。 Using this model, Professor Zheng Ping's research group used neural circuit tracing and intervention techniques to study the neural circuits in which the lateral hypothalamus (LH) participates in scene reactivation of addictive memory, and the results show that the scene can activate LH glutamatergic neurons, and inhibition of LH glutamatergic neurons can significantly inhibit scene reactivation of addictive memory.
D1 receptor spiny neurons (D1-MSNs) projected from the nucleus accumbens core region (NAcC) to LH are important upstream circuits that activate LH glutamatergic neurons; The D1-MSNs projected by NAcC to LH activate LH glutamatergic neurons by undoing the inhibition of LH local GABAergic neurons on LH glutamatergic neurons, thereby participating in the scene reactivation
of addictive memories.

This project is supported
by the National Natural Science Foundation of China Innovation Group Project, the National Natural Science Foundation of China Key Project, and the 2030 Brain Program.