Source︱ "Logical Neuroscience" sister number "Lanhan Life Science"

Written by Zhao Zhengdong

Editor in charge︱Fang Yiyi, Wang Sizhen

Editors︱Fang Yiyi, Yang Binwei

Drug addiction is a chronic relapsing brain disease characterized by compulsive seeking and use of drugs and loss of control over drug use

So, which neurons in the nucleus accumbens are important in regulating drug addiction? Related research has focused on medium spiny neurons (MSN), which account for more than 90% of the neurons in the nucleus accumbens

In August 2022, Professor Zhang Yi's laboratory at Harvard Medical School-Boston Children's Hospital published a research titled "A molecularly defined D1 medium spiny neuron subtype negatively regulates cocaine addiction" in the journal Science Advance, which systematically studied a Physiological functions and circuit mechanisms of neurons that are important regulators of addiction-related behaviors

 

The laboratory constructed the nucleus accumbens cell map in the early stage [4], and analyzed the gene expression and spatial distribution of different MSN subtypes in detail.

 

Figure 1.

(Image source: Zheng-dong Zhao et al, Sci Adv, 2022)

The authors then used neural circuit approaches such as optogenetics and chemogenetics to directly manipulate the activity of Tac2 neurons to observe behavioral changes in mice in a cocaine addiction-related paradigm

 

Figure 2 NAc Tac2 ⁺neurons bidirectionally modulate drug addiction-related behavior

(Image source: Zheng-dong Zhao et al, Sci Adv, 2022)

Finally, the authors investigated the downstream neural circuits that Tac2 neurons regulate behaviors associated with cocaine addiction

Conclusion and discussion, inspiration and prospect.
In conclusion, this article describes a subgroup of nucleus accumbens MSNs that express Tac2 gene specifically in both rodents and primates ^.
Activity dynamics during cocaine drug treatment and cocaine place preference training were found to be inversely correlated with cocaine-related behavior
.

Subsequently, the authors used optogenetics and chemogenetics to directly manipulate Tac2 ⁺ neuron activity and found that activation of Tac2 neurons attenuated cocaine-induced place preference and cocaine self-administration behavior
.

Further, the authors found that the lateral hypothalamus mediates the modulation of cocaine-addicted behaviors by Tac2 ⁺ neurons
.

These findings suggest that the classical "dichotomous model" is insufficient to adequately explain the structural and functional diversity of the nucleus accumbens, and that its different cellular subtypes may assume different functions
.

However, this work also raises further questions, such as what is the molecular mechanism by which Tac2 ⁺ neurons work? What is the function of other non-Tac2+ cell subtypes in the nucleus accumbens? How are their functions effectively organized and interact to function? Does the distribution and function of cellular subtypes within the nucleus accumbens have topology, etc.
? These issues are for further study
.

Taken together, this work provides new evidence for understanding the structural-functional diversity of the nucleus accumbens, providing new clues for understanding and intervening in drug addiction
.

Original link:research was done in the laboratory of Professor Yi Zhang at Boston Children's Hospital, Harvard Medical School
.

Dr.
Zhao Zhengdong is the first author of the study, and Professor Zhang Yi is the corresponding author
.

Corresponding author: Prof.
Zhang Yi; First author: Dr.
Zhao Zhengdong

(Photo provided by: Zhang Yi Laboratory)

Zhang Yi's laboratory currently has a number of vacancies for postdoctoral fellows in neurobiology.
The research directions include: brain cell heterogeneity, neuroepigenetics, neuronal circuitry mechanisms of pain and addiction.
Doctors who are interested in joining Zhang Yi's laboratory, please learn more: https:/ /www.
zhanglab.
tch.
harvard.
edu/
.

Selected past articles

【1】J Infect︱Wang Yifei's team revealed that the highly expressed gene MAMDC2 in Alzheimer's disease microglia positively regulates the innate antiviral response to neurotropic virus infection

【2】Sci Adv︱Xia Kun/Shen Yiping/Guo Hui Reveal the relationship between key regulatory genes of stress granules and neurodevelopmental disorders

【3】Cell Prolif︱Lai Liangxue/Zhang Kun/Zou Qingjian team successfully constructed a technical system for safe and efficient directional induction of motor neurons in vivo

【4】Nat Commun︱Peng Yueqing's team discovered a new brain area that controls non-REM sleep

【5】eClinicalMedicine︱Wang Qing’s team reported Parkinson’s disease dementia related index determination: quantitative EEG, serum metabolism and inflammation

【6】Cell Biosci | Wang Yongjun's research group reveals the molecular mechanism of D-type dopachrome isomerase-mediated inflammatory response in injured spinal cord

【7】Neuron｜Hu Yang's group revealed a large number of genes that promote optic nerve regeneration and their significant neuroprotective effects in glaucoma mice

【8】Cereb Cortex︱Zhang Yuxuan's research group reveals the neurophysiological evidence of task modulation in speech processing

[9] Trends Cogn Sci︱Jiang Qiu team writes opinion articles on creative problem solving in knowledge-rich fields

【10】Front Aging Neurosci︱Hongmei Yu's team constructed a hierarchical multi-classification diagnosis framework for AD based on imaging features and clinical information

Recommended high-quality scientific research training courses

【1】Training course︱R language clinical prediction biomedical statistics special training

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References (swipe up and down to read) 

[1] Cami, J.
& Farré, M.
Drug addiction.
New England Journal of Medicine 349, 975-986 (2003).

[2] Lobo, MK et al.
Cell type–specific loss of BDNF signaling mimics optogenetic control of cocaine reward.
Science 330, 385-390 (2010).

[3] Soares-Cunha, C.
et al.
Nucleus accumbens medium spiny neurons subtypes signal both reward and aversion.
Mol Psychiatry 25, 3241–3255, doi:10.
1038/s41380-019-0484-3 (2019).

[4] Chen, R.
et al.
Decoding molecular and cellular heterogeneity of mouse nucleus accumbens.
Nat Neurosci, doi:10.
1038/s41593-021-00938-x (2021).

[5] He, J.
et al.
Transcriptional and anatomical diversity of medium spiny neurons in the primate striatum.
Curr Biol, https://doi.
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cub.
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End of this article