2. Academic Validation
  3. Roles of nucleus accumbens shell small-conductance calcium-activated potassium channels in the conditioned fear freezing

Roles of nucleus accumbens shell small-conductance calcium-activated potassium channels in the conditioned fear freezing

  • J Psychiatr Res. 2023 May 17;163:180-194. doi: 10.1016/j.jpsychires.2023.05.057.
Minglong Zhang 1,  Yixiao Luo 2,  Jian Wang 1,  Yufei Sun 1,  Bing Xie 1,  Ludi Zhang 1,  Bin Cong 1,  Chunling Ma 3,  Di Wen 4
Affiliations

Affiliations

  • 1 College of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, Hebei Province, Shijiazhuang, 050017, PR China.
  • 2 Hunan Province People's Hospital, The First-Affiliated Hospital of Hunan Normal University, Changsha, 410081, PR China.
  • 3 College of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, Hebei Province, Shijiazhuang, 050017, PR China. Electronic address: chunlingma@126.com.
  • 4 College of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, Hebei Province, Shijiazhuang, 050017, PR China. Electronic address: wendi01125@126.com.
PMID: 37216772 DOI: 10.1016/j.jpsychires.2023.05.057
Abstract

Background: Posttraumatic stress disorder (PTSD), a psychiatric disorder caused by stressful events, is characterized by long-lasting fear memory. The nucleus accumbens shell (NAcS) is a key brain region that regulates fear-associated behavior. Small-conductance calcium-activated potassium channels (SK channels) play a key role in regulating the excitability of NAcS medium spiny neurons (MSNs) but their mechanisms of action in fear freezing are unclear.

Method: We established an animal model of traumatic memory using conditioned fear freezing paradigm, and investigated the alterations in SK channels of NAc MSNs subsequent to fear conditioning in mice. We then utilized an adeno-associated virus (AAV) transfection system to overexpress the SK3 subunit and explore the function of the NAcS MSNs SK3 channel in conditioned fear freezing.

Results: Fear conditioning activated NAcS MSNs with enhanced excitability and reduced the SK channel-mediated medium after-hyperpolarization (mAHP) amplitude. The expression of NAcS SK3 were also reduced time-dependently. The overexpression of NAcS SK3 impaired conditioned fear consolidation without affecting conditioned fear expression, and blocked fear conditioning-induced alterations in NAcS MSNs excitability and mAHP amplitude. Additionally, the amplitudes of mEPSC, AMPAR/NMDAR ratio, and membrane surface GluA1/A2 expression in NAcS MSNs was increased by fear conditioning and returned to normal levels upon SK3 overexpression, indicating that fear conditioning-induced decrease of SK3 expression caused postsynaptic excitation by facilitating AMPAR transmission to the membrane.

Conclusion: These findings show that the NAcS MSNs SK3 channel plays a critical role in conditioned fear consolidation and that it may influence PTSD pathogenesis, making it a potential therapeutic target against PTSD.

Keywords

AMPAR transmission; Conditioned fear freezing; Consolidation; MSNs excitability; Nucleus accumbens shell; SK3 channel.

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