2. Academic Validation
  3. Inhibition of RtTg neurons reverses methamphetamine-induced attention deficits

Inhibition of RtTg neurons reverses methamphetamine-induced attention deficits

  • Acta Neuropathol Commun. 2024 Nov 22;12(1):179. doi: 10.1186/s40478-024-01890-0.
Xiaotian Qu 1 2,  Pingyuan Yang 3,  Rongwei Zhai 4,  Zhi-Qi Xiong 5 6 7
Affiliations

Affiliations

  • 1 Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai, 200031, China.
  • 2 University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 3 Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200031, China.
  • 4 Lin Gang Laboratory, Shanghai, 200031, China. zhairw@lglab.ac.cn.
  • 5 Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai, 200031, China. xiongzhiqi@ion.ac.cn.
  • 6 University of Chinese Academy of Sciences, Beijing, 100049, China. xiongzhiqi@ion.ac.cn.
  • 7 Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shanghai, 201210, China. xiongzhiqi@ion.ac.cn.
PMID: 39578917 DOI: 10.1186/s40478-024-01890-0
Abstract

Chronic methamphetamine (METH) use, a prevalent psychostimulant, is known to impair attention, yet the cellular mechanisms driving these deficits remain poorly understood. Here, we employed a rat model of repeated passive METH injections and evaluated attentional performance using the 5-choice serial reaction time task (5-CSRTT). Using single-nucleus RNA Sequencing, immunofluorescence and in situ hybridization, we characterized the response of neurons in the reticulotegmental nucleus (RtTg) to METH exposure. Our results indicate that METH exposure disrupts RtTg neurons at the transcriptional level and results in an increased activation ratio of RtTg under 5-CSRTT conditions. Crucially, chemogenetic inactivation of these neurons or RtTg lesion attenuated METH-induced attention deficits, whereas their activation reproduced the deficits. These findings underscore the critical role of RtTg neurons in mediating METH-induced attention deficits, positioning RtTg as a promising therapeutic target for the treatment of attention deficits linked to chronic METH use.

Keywords

Attention; Designer receptors exclusively activated by designer drugs (DREADD); Five-choice serial reaction time task (5-CSRTT); Methamphetamine (METH); Reticulotegmental nucleus (RtTg); Single-nuclei RNA sequencing (snRNA-seq).

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z